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Sample records for lysr family transcriptional

  1. The Sinorhizobium meliloti LysR family transcriptional factor LsrB is involved in regulation of glutathione biosynthesis.

    Science.gov (United States)

    Lu, Dawei; Tang, Guirong; Wang, Dong; Luo, Li

    2013-10-01

    Glutathione, a key antioxidant in Sinorhizobium meliloti, is required for the development of alfalfa (Medicago sativa) nitrogen-fixing nodules. This tripeptide can be synthesized by both γ-glutamyl cysteine synthetase (GshA) and glutathione synthetase (GshB) in Escherichia coli and S. meliloti. Genetic evidence has indicated that the null mutant of S. meliloti gshA or gshB1 does not establish efficient symbiosis on alfalfa. However, the transcriptional regulation of gshA and gshB has not been well understood. Here, S. meliloti LsrB, a member of LysR family transcriptional factors, was found to positively regulate glutathione biosynthesis by activating the transcription of gshA and gshB1 under both free-living and symbiotic conditions. The decrease in glutathione production in the lsrB in-frame deletion mutant (lsrB1-2) was determined by using quadrupole time-of-flight liquid chromatography-mass spectrometry. The expression of gshA and gshB1 was correspondingly reduced in the mutant under free-living and symbiotic conditions by analyses of real-time quantitative reverse transcription-polymerase chain reaction and promoter-GUS fusions. Interestingly, LsrB positively regulated the transcription of oxyR, which encodes another member of LysR family regulators and responds to oxidative stresses in S. meliloti. The oxyR null mutant produced less glutathione, in which the transcription of gshA was consistently down-regulated. These findings demonstrate that glutathione biosynthesis is positively regulated by both LsrB and OxyR in S. meliloti.

  2. The solution configurations of inactive and activated DntR have implications for the sliding dimer mechanism of LysR transcription factors.

    Science.gov (United States)

    Lerche, Michael; Dian, Cyril; Round, Adam; Lönneborg, Rosa; Brzezinski, Peter; Leonard, Gordon A

    2016-01-28

    LysR Type Transcriptional Regulators (LTTRs) regulate basic metabolic pathways or virulence gene expression in prokaryotes. Evidence suggests that the activation of LTTRs involves a conformational change from an inactive compact apo- configuration that represses transcription to an active, expanded holo- form that promotes it. However, no LTTR has yet been observed to adopt both configurations. Here, we report the results of structural studies of various forms of the LTTR DntR. Crystal structures of apo-DntR and of a partially autoinducing mutant H169T-DntR suggest that active and inactive DntR maintain a compact homotetrameric configuration. However, Small Angle X-ray Scattering (SAXS) studies on solutions of apo-, H169T- and inducer-bound holo-DntR indicate a different behaviour, suggesting that while apo-DntR maintains a compact configuration in solution both H169T- and holo-DntR adopt an expanded conformation. Models of the SAXS-obtained solution conformations of apo- and holo-DntR homotetramers in complex with promoter-operator region DNA are consistent with previous observations of a shifting of LTTR DNA binding sites upon activation and a consequent relaxation in the bend of the promoter-operator region DNA. Our results thus provide clear evidence at the molecular level which strongly supports the 'sliding dimer' hypothesis concerning LTTR activation mechanisms.

  3. The hexA gene of Erwinia carotovora encodes a LysR homologue and regulates motility and the expression of multiple virulence determinants.

    Science.gov (United States)

    Harris, S J; Shih, Y L; Bentley, S D; Salmond, G P

    1998-05-01

    We have identified a gene important for the regulation of exoenzyme virulence factor synthesis in the plant pathogen Erwinia carotovora ssp. carotovora (Ecc) and virulence and motility in Erwinia carotovora ssp. atroseptica (Eca). This gene, hexA (hyperproduction of exoenzymes), is a close relative of the Erwinia chrysanthemi (Echr) gene pecT and encodes a member of the LysR family of transcriptional regulators. hexA mutants in both Ecc and Eca produce abnormally high levels of the exoenzyme virulence factors pectate lyase, cellulase and protease. In addition, Eca hexA mutants show increased expression of the fliA and fliC genes and hypermotility. Consistent with a role as a global regulator, expression of hexA from even a low-copy plasmid can suppress exoenzyme production in Ecc and Eca and motility in Eca. Production of the quorum-sensing pheromone OHHL in Ecc hexA is higher throughout the growth curve compared with the wild-type strain. Overexpression of Ecc hexA also caused widespread effects in several strains of the opportunistic human pathogen, Serratia. Low-copy hexA expression resulted in repression of exoenzyme, pigment and antibiotic production and repression of the spreading phenotype. Finally, mutations in hexA were shown to increase Ecc or Eca virulence in planta.

  4. The Lrp family of transcriptional regulators

    NARCIS (Netherlands)

    Brinkman, A.B.; Ettema, T.J.G.; Vos, de W.M.; Oost, van der J.

    2003-01-01

    Genome analysis has revealed that members of the Lrp family of transcriptional regulators are widely distributed among prokaryotes, both bacteria and archaea. The archetype Leucine-responsive Regulatory Protein from Escherichia coli is a global regulator involved in modulating a variety of metabolic

  5. A LysR-family transcriptional regulator required for virulence in Brucella abortus is highly conserved among the α-proteobacteria.

    Science.gov (United States)

    Sheehan, Lauren M; Budnick, James A; Blanchard, Catlyn; Dunman, Paul M; Caswell, Clayton C

    2015-10-01

    Small RNAs are principal elements of bacterial gene regulation and physiology. Two small RNAs in Brucella abortus, AbcR1 and AbcR2, are required for wild-type virulence. Examination of the abcR loci revealed the presence of a gene encoding a LysR-type transcriptional regulator flanking abcR2 on chromosome 1. Deletion of this lysR gene (bab1_1517) resulted in the complete loss of abcR2 expression while no difference in abcR1 expression was observed. The B. abortus bab1_1517 mutant strain was significantly attenuated in macrophages and mice, and bab1_1517 was subsequently named vtlR for virulence-associated transcriptional LysR-family regulator. Microarray analysis revealed three additional genes encoding small hypothetical proteins also under the control of VtlR. Electrophoretic mobility shift assays demonstrated that VtlR binds directly to the promoter regions of abcR2 and the three hypothetical protein-encoding genes, and DNase I footprint analysis identified the specific nucleotide sequence in these promoters that VtlR binds to and drives gene expression. Strikingly, orthologs of VtlR are encoded in a wide range of host-associated α-proteobacteria, and it is likely that the VtlR genetic system represents a common regulatory circuit critical for host-bacterium interactions.

  6. Transcription Factor Families Regulate the Anthocyanin Biosynthetic Pathway in Capsicum

    Science.gov (United States)

    Anthocyanin structural gene transcription requires the expression of at least one member of each of three transcription factor families - MYC, MYB and WD40. These transcription factors form a complex that binds to structural gene promoters, thereby modulating gene expression. Capsicum annuum display...

  7. Cross-Family Transcription Factor Interactions

    NARCIS (Netherlands)

    Bemer, Marian; Dijk, van Aalt-Jan; Immink, Richard G.H.; Angenent, Gerco C.

    2017-01-01

    Specific and dynamic gene expression strongly depends on transcription factor (TF) activity and most plant TFs function in a combinatorial fashion. They can bind to DNA and control the expression of the corresponding gene in an additive fashion or cooperate by physical interactions, forming larger p

  8. The WRKY transcription factor family in Brachypodium distachyon

    Directory of Open Access Journals (Sweden)

    Tripathi Prateek

    2012-06-01

    Full Text Available Abstract Background A complete assembled genome sequence of wheat is not yet available. Therefore, model plant systems for wheat are very valuable. Brachypodium distachyon (Brachypodium is such a system. The WRKY family of transcription factors is one of the most important families of plant transcriptional regulators with members regulating important agronomic traits. Studies of WRKY transcription factors in Brachypodium and wheat therefore promise to lead to new strategies for wheat improvement. Results We have identified and manually curated the WRKY transcription factor family from Brachypodium using a pipeline designed to identify all potential WRKY genes. 86 WRKY transcription factors were found, a total higher than all other current databases. We therefore propose that our numbering system (BdWRKY1-BdWRKY86 becomes the standard nomenclature. In the JGI v1.0 assembly of Brachypodium with the MIPS/JGI v1.0 annotation, nine of the transcription factors have no gene model and eleven gene models are probably incorrectly predicted. In total, twenty WRKY transcription factors (23.3% do not appear to have accurate gene models. To facilitate use of our data, we have produced The Database of Brachypodium distachyon WRKY Transcription Factors. Each WRKY transcription factor has a gene page that includes predicted protein domains from MEME analyses. These conserved protein domains reflect possible input and output domains in signaling. The database also contains a BLAST search function where a large dataset of WRKY transcription factors, published genes, and an extensive set of wheat ESTs can be searched. We also produced a phylogram containing the WRKY transcription factor families from Brachypodium, rice, Arabidopsis, soybean, and Physcomitrella patens, together with published WRKY transcription factors from wheat. This phylogenetic tree provides evidence for orthologues, co-orthologues, and paralogues of Brachypodium WRKY transcription factors

  9. Transcription-dependent degradation controls the stability of the SREBP family of transcription factors.

    Science.gov (United States)

    Sundqvist, Anders; Ericsson, Johan

    2003-11-25

    Cholesterol metabolism is tightly controlled by members of the sterol regulatory element-binding protein (SREBP) family of transcription factors. Here we demonstrate that the ubiquitination and degradation of SREBPs depend on their transcriptional activity. Mutations in the transactivation or DNA-binding domains of SREBPs inhibit their transcriptional activity and stabilize the proteins. The transcriptional activity and degradation of these mutants are restored when fused to heterologous transactivation or DNA-binding domains. When SREBP1a was fused to the DBD of Gal4, the ubiquitination and degradation of the fusion protein depended on coexpression of a promoter-reporter gene containing Gal4-binding sites. In addition, disruption of the interaction between WT SREBP and endogenous p300/CBP resulted in inhibition of SREBP-dependent transcription and stabilization of SREBP. Chemical inhibitors of transcription reduced the degradation of transcriptionally active SREBP1a, whereas they had no effect on the stability of transcriptionally inactive mutants, demonstrating that transcriptional activation plays an important role in the degradation of SREBPs. Thus, transcription-dependent degradation of SREBP constitutes a feedback mechanism to regulate the expression of genes involved in cholesterol metabolism and may represent a general mechanism to regulate the duration of transcriptional responses.

  10. Global transcriptional regulator TrmB family members in prokaryotes.

    Science.gov (United States)

    Kim, Minwook; Park, Soyoung; Lee, Sung-Jae

    2016-10-01

    Members of the TrmB family act as global transcriptional regulators for the activation or repression of sugar ABC transporters and central sugar metabolic pathways, including glycolytic, gluconeogenic, and other metabolic pathways, and also as chromosomal stabilizers in archaea. As a relatively newly classified transcriptional regulator family, there is limited experimental evidence for their role in Thermococcales, halophilic archaeon Halobacterium salinarum NRC1, and crenarchaea Sulfolobus strains, despite being one of the extending protein families in archaea. Recently, the protein structures of Pyrococcus furiosus TrmB and TrmBL2 were solved, and the transcriptomic data uncovered by microarray and ChIP-Seq were published. In the present review, recent evidence of the functional roles of TrmB family members in archaea is explained and extended to bacteria.

  11. CRTR-1, a developmentally regulated transcriptional repressor related to the CP2 family of transcription factors.

    Science.gov (United States)

    Rodda, S; Sharma, S; Scherer, M; Chapman, G; Rathjen, P

    2001-02-02

    CP2-related proteins comprise a family of DNA-binding transcription factors that are generally activators of transcription and expressed ubiquitously. We reported a differential display polymerase chain reaction fragment, Psc2, which was expressed in a regulated fashion in mouse pluripotent cells in vitro and in vivo. Here, we report further characterization of the Psc2 cDNA and function. The Psc2 cDNA contained an open reading frame homologous to CP2 family proteins. Regions implicated in DNA binding and oligomeric complex formation, but not transcription activation, were conserved. Psc2 expression in vivo during embryogenesis and in the adult mouse demonstrated tight spatial and temporal regulation, with the highest levels of expression in the epithelial lining of distal convoluted tubules in embryonic and adult kidneys. Functional analysis demonstrated that PSC2 repressed transcription 2.5-15-fold when bound to a heterologous promoter in ES, 293T, and COS-1 cells. The N-terminal 52 amino acids of PSC2 were shown to be necessary and sufficient for this activity and did not share obvious homology with reported repressor motifs. These results represent the first report of a CP2 family member that is expressed in a developmentally regulated fashion in vivo and that acts as a direct repressor of transcription. Accordingly, the protein has been named CP2-Related Transcriptional Repressor-1 (CRTR-1).

  12. The AP2/EREBP family of plant transcription factors.

    Science.gov (United States)

    Riechmann, J L; Meyerowitz, E M

    1998-06-01

    AP2 (APETALA2) and EREBPs (ethylene-responsive element binding proteins) are the prototypic members of a family of transcription factors unique to plants, whose distinguishing characteristic is that they contain the so-called AP2 DNA-binding domain. AP2/ REBP genes form a large multigene family, and they play a variety of roles throughout the plant life cycle: from being key regulators of several developmental processes, like floral organ identity determination or control of leaf epidermal cell identity, to forming part of the mechanisms used by plants to respond to various types of biotic and environmental stress. The molecular and biochemical characteristics of the AP2/EREBP transcription factors and their diverse functions are reviewed here, and this multigene family is analyzed within the context of the Arabidopsis thaliana genome sequence project.

  13. Early evolution of the T-box transcription factor family

    Science.gov (United States)

    Sebé-Pedrós, Arnau; Ariza-Cosano, Ana; Weirauch, Matthew T.; Leininger, Sven; Yang, Ally; Torruella, Guifré; Adamski, Marcin; Adamska, Maja; Hughes, Timothy R.; Gómez-Skarmeta, José Luis; Ruiz-Trillo, Iñaki

    2013-01-01

    Developmental transcription factors are key players in animal multicellularity, being members of the T-box family that are among the most important. Until recently, T-box transcription factors were thought to be exclusively present in metazoans. Here, we report the presence of T-box genes in several nonmetazoan lineages, including ichthyosporeans, filastereans, and fungi. Our data confirm that Brachyury is the most ancient member of the T-box family and establish that the T-box family diversified at the onset of Metazoa. Moreover, we demonstrate functional conservation of a homolog of Brachyury of the protist Capsaspora owczarzaki in Xenopus laevis. By comparing the molecular phenotype of C. owczarzaki Brachyury with that of homologs of early branching metazoans, we define a clear difference between unicellular holozoan and metazoan Brachyury homologs, suggesting that the specificity of Brachyury emerged at the origin of Metazoa. Experimental determination of the binding preferences of the C. owczarzaki Brachyury results in a similar motif to that of metazoan Brachyury and other T-box classes. This finding suggests that functional specificity between different T-box classes is likely achieved by interaction with alternative cofactors, as opposed to differences in binding specificity. PMID:24043797

  14. Expression analysis of TALE family transcription factors during avian development.

    Science.gov (United States)

    Coy, Sarah E; Borycki, Anne-Gaëlle

    2010-04-01

    The TALE family of homeodomain containing transcription factors consists of the Meis, Prep and Tgif, and the Pbx subfamily of proteins. Several TALE orthologues have been identified in amniotes, but no comprehensive analysis of their expression pattern during embryogenesis has been performed. Here, we report on TALE gene expression in the avian embryo. During embryonic development, Pbx genes are predominantly expressed in the neural ectoderm and paraxial mesoderm, although Pbx3 is restricted to the intermediate and lateral mesoderm, and anterior central nervous system. Members of the Meis, Prep, and Tgif subfamilies are expressed at high levels in the paraxial mesoderm, and display differential expression along the anterior-posterior and dorsoventral axes of the developing neural tube. Overall the expression patterns reported in this study are consistent with the known function of the TALE gene family in controlling early patterning of limb, neural tube and paraxial mesoderm tissues during embryogenesis.

  15. Characteristics of the LrhA subfamily of transcriptional regulators from Sinorhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    Mingsheng Qi; Li Luo; Haiping Cheng; Jiabi Zhu; Guanqiao Yu

    2008-01-01

    In our previous work, we identified 94 putative genes encoding LysR-type transcriptional regulators from Sinorhizobium meliloti. All of these putative lysR genes were mutagenized using plasmid insertions to determine their phenotypes. Six LysR-type regulators, encoded by mutants SMa1979, SMb20715, SMc00820, SMc04163, SMc03975,and SMc04315, showed similar amino acid sequences (30%)and shared the conserved DNA-binding domain with LrhA,HexA, or DgdR. Phenotype analysis of these gene mutants indicated that the regulators control the swimming behaviors of the bacteria, production of quorum-sensing signals, and secretion of extracellular proteins. These characteristics are very similar to those of LrhA, HexA, and DgdR.Thus, we refer to this group as the LrhA subfamily. Sequence analysis showed that a great number of homologous genes of the LrhA subfamily were distributed in the α,β, and γsubdivisions of proteobacteria, and a few in actinobacteria. These findings could provide new clues to the roles of the LysR gene family.

  16. Pseudomonas aeruginosa LysR PA4203 regulator NmoR acts as a repressor of the PA4202 nmoA> gene, encoding a nitronate monooxygenase

    DEFF Research Database (Denmark)

    Vercammen, Ken; Wei, Qing; Charlier, Daniel;

    2015-01-01

    The PA4203 gene encodes a LysR regulator and lies between the ppgL gene (PA4204), which encodes a periplasmic gluconolactonase, and, in the opposite orientation, the PA4202 (nmoA) gene, coding for a nitronate monooxygenase, and ddlA (PA4201), encoding a d-alanine alanine ligase. The intergenic re...

  17. The ETS family of oncogenic transcription factors in solid tumours.

    Science.gov (United States)

    Sizemore, Gina M; Pitarresi, Jason R; Balakrishnan, Subhasree; Ostrowski, Michael C

    2017-06-01

    Findings over the past decade have identified aberrant activation of the ETS transcription factor family throughout all stages of tumorigenesis. Specifically in solid tumours, gene rearrangement and amplification, feed-forward growth factor signalling loops, formation of gain-of-function co-regulatory complexes and novel cis-acting mutations in ETS target gene promoters can result in increased ETS activity. In turn, pro-oncogenic ETS signalling enhances tumorigenesis through a broad mechanistic toolbox that includes lineage specification and self-renewal, DNA damage and genome instability, epigenetics and metabolism. This Review discusses these different mechanisms of ETS activation and subsequent oncogenic implications, as well as the clinical utility of ETS factors.

  18. Computational Analysis of the Transcriptional Regulation of the Actin Family

    Institute of Scientific and Technical Information of China (English)

    郑家顺; 吴加金; 孙之荣

    2002-01-01

    Transcriptional regulation is a very important regulatory step in the regulation of gene expression. Transcription factors (TFs) play an important role in controlling the temporal special specificity of gene expression. The regulation area of actin genes was analyzed statistically to predict the transcription factor binding sites in the regulatory area. A group of transcription factors located in most of the sequences is believed to play an important role in co-regulating the expression of actin genes.

  19. Integration and diversity of the regulatory network composed of Maf and CNC families of transcription factors.

    Science.gov (United States)

    Motohashi, Hozumi; O'Connor, Tania; Katsuoka, Fumiki; Engel, James Douglas; Yamamoto, Masayuki

    2002-07-10

    Recent progress in the analysis of transcriptional regulation has revealed the presence of an exquisite functional network comprising the Maf and Cap 'n' collar (CNC) families of regulatory proteins, many of which have been isolated. Among Maf factors, large Maf proteins are important in the regulation of embryonic development and cell differentiation, whereas small Maf proteins serve as obligatory heterodimeric partner molecules for members of the CNC family. Both Maf homodimers and CNC-small Maf heterodimers bind to the Maf recognition element (MARE). Since the MARE contains a consensus TRE sequence recognized by AP-1, Jun and Fos family members may act to compete or interfere with the function of CNC-small Maf heterodimers. Overall then, the quantitative balance of transcription factors interacting with the MARE determines its transcriptional activity. Many putative MARE-dependent target genes such as those induced by antioxidants and oxidative stress are under concerted regulation by the CNC family member Nrf2, as clearly proven by mouse germline mutagenesis. Since these genes represent a vital aspect of the cellular defense mechanism against oxidative stress, Nrf2-null mutant mice are highly sensitive to xenobiotic and oxidative insults. Deciphering the molecular basis of the regulatory network composed of Maf and CNC families of transcription factors will undoubtedly lead to a new paradigm for the cooperative function of transcription factors.

  20. The TrmB family: a versatile group of transcriptional regulators in Archaea.

    Science.gov (United States)

    Gindner, Antonia; Hausner, Winfried; Thomm, Michael

    2014-09-01

    Microbes are organisms which are well adapted to their habitat. Their survival depends on the regulation of gene expression levels in response to environmental signals. The most important step in regulation of gene expression takes place at the transcriptional level. This regulation is intriguing in Archaea because the eu-karyotic-like transcription apparatus is modulated by bacterial-like transcription regulators. The transcriptional regulator of mal operon (TrmB) family is well known as a very large group of regulators in Archaea with more than 250 members to date. One special feature of these regulators is that some of them can act as repressor, some as activator and others as both repressor and activator. This review gives a short updated overview of the TrmB family and their regulatory patterns in different Archaea as a lot of new data have been published on this topic since the last review from 2008.

  1. The TEAD/TEF Family Protein Scalloped Mediates Transcriptional Output of the Hippo Growth-Regulatory Pathway

    National Research Council Canada - National Science Library

    Wu, Shian; Liu, Yi; Zheng, Yonggang; Dong, Jixin; Pan, Duojia

    2008-01-01

    .... Here we identify the TEAD/TEF family protein Scalloped (Sd) as a DNA-binding transcription factor that partners with Yki to mediate the transcriptional output of the Hpo growth-regulatory pathway. The diap1 (th...

  2. Determination of specificity influencing residues for key transcription factor families

    DEFF Research Database (Denmark)

    Patel, Ronak Y.; Garde, Christian; Stormo, Gary D.

    2015-01-01

    -dimensional structure of protein. Structural restraints on the evolution of the amino-acid sequence lead to identification of false SIRs. In this manuscript we extended three methods (direct information, PSICOVand adjusted mutual information) that have been used to disentangle spurious indirect protein residue......-residue contacts from direct contacts, to identify SIRs from joint alignments of amino-acids and specificity. We predicted SIRs for homeodomain (HD), helix-loop-helix, LacI and GntR families of TFs using these methods and compared to MI. Using various measures, we show that the performance of these three methods...

  3. CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties

    DEFF Research Database (Denmark)

    Lillestøl, Reidun K; Shah, Shiraz Ali; Brügger, Kim

    2009-01-01

    Summary CRISPRs of Sulfolobus fall into three main families based on their repeats, leader regions, associated cas genes, and putative recognition sequences on viruses and plasmids. Spacer sequence matches to different viruses and plasmids of the Sulfolobales revealed some bias particularly...... for family III CRISPRs. Transcription occurs on both strands of the five repeat-clusters of Sulfolobus acidocaldarius and a repeat-cluster of the conjugative plasmid pKEF9. Leader strand transcripts cover whole repeat-clusters and are processed mainly from the 3'-end, within repeats, yielding heterogeneous...

  4. Characterization of the Far Transcription Factor Family in Aspergillus flavus

    Science.gov (United States)

    Luo, Xingyu; Affeldt, Katharyn J.; Keller, Nancy P.

    2016-01-01

    Metabolism of fatty acids is a critical requirement for the pathogenesis of oil seed pathogens including the fungus Aspergillus flavus. Previous studies have correlated decreased ability to grow on fatty acids with reduced virulence of this fungus on host seed. Two fatty acid metabolism regulatory transcription factors, FarA and FarB, have been described in other filamentous fungi. Unexpectedly, we find A. flavus possesses three Far homologs, FarA, FarB, and FarC, with FarA and FarC showing a greater protein similarity to each other than FarB. farA and farB are located in regions of colinearity in all Aspergillus spp. sequenced to date, whereas farC is limited to a subset of species where it is inserted in an otherwise colinear region in Aspergillus genomes. Deletion and overexpression (OE) of farA and farB, but not farC, yielded mutants with aberrant growth patterns on specific fatty acids as well as altered expression of genes involved in fatty acid metabolism. Marked differences included significant growth defects of both ∆farA and ∆farB on medium-chain fatty acids and decreased growth of OE::farA on unsaturated fatty acids. Loss of farA diminished expression of mitochondrial β-oxidation genes whereas OE::farA inhibited expression of genes involved in unsaturated fatty acid catabolism. FarA also positively regulated the desaturase genes required to generate polyunsaturated fatty acids. Aflatoxin production on toxin-inducing media was significantly decreased in the ∆farB mutant and increased in the OE::farB mutant, with gene expression data supporting a role for FarB in tying β-oxidation processes with aflatoxin accumulation. PMID:27534569

  5. Ikaros family transcription factors expression in rat thymus: detection of impaired development.

    Science.gov (United States)

    Paradzik, M; Novak, S; Mokrovic, G; Bordukalo Niksic, T; Heckel, D; Stipic, J; Pavicic Baldani, D; Cicin-Sain, L; Antica, M

    2012-01-01

    The expression of Ikaros family transcription factors and consequently their signalling pathway is limiting for hematopoietic and lymphocyte development in mice and human. Due to their importance, these transcription factors are highly homologous between species. As an initial approach to examining the possible involvement of Ikaros transcription factors in pathogenesis of rat lymphoid development, we analyzed the expression of all known Ikaros family members, Ikaros, Aiolos, Helios, Eos and Pegasus in the rat thymus. We established a semi-quantitative RT-PCR to detect mRNA of each transcription factor. For the first time we give evidence of the expression of Ikaros family transcription factors in the rat thymus. Further, we evaluated whether their mRNA expression was succumbed to changes when the rats were exposed to ethanol, as a known debilitating agent during development. Therefore we analyzed the thymus of adult rats whose mothers were forced to drink ethanol during gestation, to detect possible changes in thymus mRNA expression levels of Ikaros, Aiolos, Helios, Eos and Pegasus. We found that rats prenatally exposed to ethanol show a slightly higher expression of Ikaros family transcription factors in the adult thymus when compared to control rats, but these differences were not statistically significant. We further studied the distribution of the major lymphocyte subpopulations in the rat thymus according to CD3, CD4 and CD8 expression by four color flow cytometry. We found a higher incidence of CD3 positive cells in the double positive, CD4+CD8+ thymic subpopulation of rats prenatally exposed to ethanol when compared to non-exposed animals. Our findings indicate that ethanol exposure of pregnant rats might influence the development of CD3 positive cells in the thymus of the offspring but this result should be further tackled at the level of transcription factor expression.

  6. bZIPs and WRKYs: two large transcription factor families executing two different functional strategies

    Directory of Open Access Journals (Sweden)

    Carles eMarco Llorca

    2014-04-01

    Full Text Available bZIPs and WRKYs are two important plant transcription factor families regulating diverse developmental and stress-related processes. Since a partial overlap in these biological processes is obvious, it can be speculated that they fulfill non-redundant functions in a complex regulatory network. Here, we focus on the regulatory mechanisms that are so far described for bZIPs and WRKYs. bZIP factors need to heterodimerize for DNA-binding and regulation of transcription, and based on a bioinformatics approach, bZIPs can build up more than the double of protein interactions than WRKYs. In contrast, an enrichment of the WRKY DNA-binding motifs can be found in WRKY promoters, a phenomenon which is not observed for the bZIP family. Thus, the two transcription factor families follow two different functional strategies in which WRKYs regulate each other’s transcription in a transcriptional network whereas bZIP action relies on intensive heterodimerization.

  7. Modulation of CP2 family transcriptional activity by CRTR-1 and sumoylation.

    Directory of Open Access Journals (Sweden)

    Sarah To

    Full Text Available CRTR-1 is a member of the CP2 family of transcription factors. Unlike other members of the family which are widely expressed, CRTR-1 expression shows specific spatio-temporal regulation. Gene targeting demonstrates that CRTR-1 plays a central role in the maturation and function of the salivary glands and the kidney. CRTR-1 has also recently been identified as a component of the complex transcriptional network that maintains pluripotency in embryonic stem (ES cells. CRTR-1 was previously shown to be a repressor of transcription. We examine the activity of CRTR-1 in ES and other cells and show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. We also demonstrate that CRTR-1 activity is regulated by sumoylation at a single major site, residue K30. These findings imply that functional redundancy with other family members may mask important roles for CRTR-1 in other tissues, including the blastocyst stage embryo and embryonic stem cells.

  8. Modulation of CP2 family transcriptional activity by CRTR-1 and sumoylation.

    Science.gov (United States)

    To, Sarah; Rodda, Stephen J; Rathjen, Peter D; Keough, Rebecca A

    2010-07-22

    CRTR-1 is a member of the CP2 family of transcription factors. Unlike other members of the family which are widely expressed, CRTR-1 expression shows specific spatio-temporal regulation. Gene targeting demonstrates that CRTR-1 plays a central role in the maturation and function of the salivary glands and the kidney. CRTR-1 has also recently been identified as a component of the complex transcriptional network that maintains pluripotency in embryonic stem (ES) cells. CRTR-1 was previously shown to be a repressor of transcription. We examine the activity of CRTR-1 in ES and other cells and show that CRTR-1 is generally an activator of transcription and that it modulates the activity of other family members, CP2, NF2d9 and altNF2d9, in a cell specific manner. We also demonstrate that CRTR-1 activity is regulated by sumoylation at a single major site, residue K30. These findings imply that functional redundancy with other family members may mask important roles for CRTR-1 in other tissues, including the blastocyst stage embryo and embryonic stem cells.

  9. The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control.

    Science.gov (United States)

    Zhang, Lei; Ren, Fangfang; Zhang, Qing; Chen, Yongbin; Wang, Bing; Jiang, Jin

    2008-03-01

    The Hippo (Hpo) signaling pathway governs cell growth, proliferation, and apoptosis by controlling key regulatory genes that execute these processes; however, the transcription factor of the pathway has remained elusive. Here we provide evidence that the TEAD/TEF family transcription factor Scalloped (Sd) acts together with the coactivator Yorkie (Yki) to regulate Hpo pathway-responsive genes. Sd and Yki form a transcriptional complex whose activity is inhibited by Hpo signaling. Sd overexpression enhances, whereas its inactivation suppresses, tissue overgrowth caused by Yki overexpression or tumor suppressor mutations in the Hpo pathway. Inactivation of Sd diminishes Hpo target gene expression and reduces organ size, whereas a constitutively active Sd promotes tissue overgrowth. Sd promotes Yki nuclear localization, whereas Hpo signaling retains Yki in the cytoplasm by phosphorylating Yki at S168. Finally, Sd recruits Yki to the enhancer of the pathway-responsive gene diap1, suggesting that diap1 is a direct transcriptional target of the Hpo pathway.

  10. Genome-wide Analysis of Plant-specific Dof Transcription Factor Family in Tomato

    Institute of Scientific and Technical Information of China (English)

    Xiaofeng Cai; Yuyang Zhang; Chanjuan Zhang; Tingyan Zhang; Tixu Hu; Jie Ye; Junhong Zhang

    2013-01-01

    The Dof (DNA binding with One Finger) family encoding single zinc finger proteins has been known as a family of plant-specific transcription factors.These transcription factors are involved in a variety of functions of importance for different biological processes in plants.In the current study,we identified 34 Dof family genes in tomato (Solanum lycopersicum L.),distributed on 11 chromosomes.A complete overview of SIDof genes in tomato is presented,including the gene structures,chromosome locations,phylogeny,protein motifs and evolution pattern.Phylogenetic analysis of 34 SlDof proteins resulted in four classes constituting six clusters.In addition,a comparative analysis between these genes in tomato,Arabidopsis (Arabidopsis thaliana L.) and rice (Oryza sativa L.) was also performed.The tomato Dof family expansion has been dated to recent duplication events,and segmental duplication is predominant for the SlDof genes.Furthermore,the SlDof genes displayed differential expression either in their transcript abundance or in their expression patterns under normal growth conditions.This is the first step towards genome-wide analyses of the Dof genes in tomato.Our study provides a very useful reference for cloning and functional analysis of the members of this gene family in tomato and other species.

  11. Hammerhead-mediated processing of satellite pDo500 family transcripts from Dolichopoda cave crickets.

    Science.gov (United States)

    Rojas, A A; Vazquez-Tello, A; Ferbeyre, G; Venanzetti, F; Bachmann, L; Paquin, B; Sbordoni, V; Cedergren, R

    2000-10-15

    This work reports the discovery and functional characterization of catalytically active hammerhead motifs within satellite DNA of the pDo500 family from several DOLICHOPODA: cave cricket species. We show that in vitro transcribed RNA of some members of this satellite DNA family do self-cleave in vitro. This self-cleavage activity is correlated with the efficient in vivo processing of long primary transcripts into monomer-sized RNA. The high sequence conservation of the satellite pDo500 DNA family among genetically isolated DOLICHOPODA: schiavazzii populations, as well as other DOLICHOPODA: species, along with the fact that satellite members are actively transcribed in vivo suggests that the hammerhead-encoding satellite transcripts are under selective pressure, perhaps because they fulfil an important physiological role or function. Remarkably, this is the third example of hammerhead ribozyme structures associated with transcribed repetitive DNA sequences from animals. The possibility that such an association may not be purely coincidental is discussed.

  12. Transcription factor-based biosensors enlightened by the analyte.

    Directory of Open Access Journals (Sweden)

    Raul eFernandez-Lopez

    2015-07-01

    Full Text Available Whole cell biosensors (WCBs have multiple applications for environmental monitoring, detecting a wide range of pollutants. WCBs depend critically on the sensitivity and specificity of the transcription factor (TF used to detect the analyte. We describe the mechanism of regulation and the structural and biochemical properties of TF families that are used, or could be used, for the development of environmental WCBs. Focusing on the chemical nature of the analyte, we review TFs that respond to aromatic compounds (XylS-AraC, XylR-NtrC and LysR, metal ions (MerR, ArsR, DtxR, Fur and NikR or antibiotics (TetR and MarR. Analyzing the structural domains involved in DNA recognition, we highlight the similitudes in the DNA binding domains (DBDs of these TF families. Opposite to DBDs, the wide range of analytes detected by TFs results in a diversity of structures at the effector binding domain (EBD. The modular architecture of TFs opens the possibility of engineering TFs with hybrid DNA and effector specificities. Yet, the lack of a crisp correlation between structural domains and specific functions makes this a challenging task.

  13. Identification of retrotransposon families and analysis of their transcriptional activation in wheat

    Institute of Scientific and Technical Information of China (English)

    TANG Yimiao; MA Youzhi; LI Liancheng; XIN Zhiyong

    2005-01-01

    Variations in the reverse transcriptase (RT) domain were analyzed to clarify retrotransposon family structure and their evolution in wheat genome. RT-PCR was conducted by using primers based on the conserved RT peptide motifs of plant retrotransposons to amplify the RT domain of retrotransposons in the seedlings of wheat line Pm97034 treated with powdery mildew fungus. High level of heterogeneity was detected in 51 (RT1-51) clones randomly selected and the identity of nucleotide sequence among them ranged from 75.4% to 97.9%. These sequences, in combination with previously identified seven representatives from wheat retrotransposon families (families 1―7), were used to construct a composite phylogenetic tree. Three new families, designated family 8 to family 10, were identified. Famliy 8 formed before divergence of the Pooideae subfamily and was regarged as an ancient retrotransposon family. Some members of family 4 and family 7 had transcriptional activativity, and were present with multiple copies in wheat and its related species.

  14. The PRR family of transcriptional regulators reflects the complexity and evolution of plant circadian clocks.

    Science.gov (United States)

    Farré, Eva M; Liu, Tiffany

    2013-10-01

    Circadian clocks are internal time-keeping mechanisms that provide an adaptive advantage by enabling organisms to anticipate daily changes and orchestrate biological processes accordingly. Circadian regulated pseudo-response regulators are key components of transcription/translation circadian networks in green alga and plants. Recent studies in Arabidopsis thaliana have shown that most of them act as transcriptional repressors and directly regulate output pathways suggesting a close relationship between the central oscillator and circadian regulated processes. Moreover, phylogenetic studies on this small gene family have shed light on the evolution of circadian clocks in the green lineage.

  15. Systematic insertion mutagenesis of GntR family transcriptional regulator genes in Sinorhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    GntR-type transcriptional regulators regulate the most diverse biological processes in bacteria. Although GntR-type transcriptional regulators consist of the second largest family of transcriptional regulators in Sinorhizobium meliloti, little is known about their functions. In this study, we investigated 54 putative genes encoding GntR family of transcriptional regulators in S. meliloti Rm1021. Secondary structure analysis of the C-terminal domain of these putative transcriptional regulators indicated that thirty-seven were members of the FadR subfamily, ten of the HutC subfamily and five of the MocR subfamily. The remaining two did not fall into any specific subfamily category, and may form two new subfamilies. The 54 gntR genes were mutagenized by plasmid insertion mutagenesis to investigate their roles. We found that, of the 54 mutants, only the gtrA1 and gtrB1 mutants had slower growth rates and cell maximal yields on both rich medium and minimal medium, and lower cell motility on swarming plate than wild type Rm1021. All mutants, with the exception of gtrA1 and gtrB1, can establish effective symbioses with alfalfa. Plants inoculated with gtrA1 and gtrB1 mutants grew shorter than those inoculated with wild type, and formed relatively smaller, round and light pink nodules, which were mainly located on lateral roots. And there was an abnormal increase in the number of nodules induced by both mutants. These results suggested that the gtrA1 and gtrB1 mutants were symbiotically deficient. Our work presents a global overview of GntR-like transcriptional regulators involved in symbiosis in S.meliloti, and provides new insight into the functions of GntR-like transcriptional regulators.

  16. MTA family of transcriptional metaregulators in mammary gland morphogenesis and breast cancer.

    Science.gov (United States)

    Singh, Rajesh R; Kumar, Rakesh

    2007-09-01

    Since breast cancer and its associated metastasis are a global health problem and a major cause of mortality among women, research efforts to understand the development, morphogenesis, and functioning of the mammary gland are a high priority. Myriad signaling pathways, transcription factors, and associated transcriptional coregulators have been identified in both normal functioning and neoplastic transformation of the mammary gland. The discovery of the metastasis tumor antigen 1 (MTA1) gene, its overexpression in cancer and metastasis and its subsequent identification as an integral part of the chromatin remodeling complex heralded extensive research on its physiological role. Subsequent identification of additional gene family members, namely MTA1s, MTA2, and MTA3, and their functions in the cell has resulted in the establishment of the significance of the MTA family. The role of these proteins in modulating hormonal responses in normal mammary glands and in breast cancer has resulted in their identification as important molecular markers and potential therapeutic targets.

  17. Regulation of the MEF2 Family of Transcription Factors by p38†

    OpenAIRE

    Zhao, Ming; New, Liguo; Kravchenko, Vladimir V.; KATO, Yutaka; Gram, Hermann; Di Padova, Franco; Olson, Eric N.; Ulevitch, Richard J.; Han, Jiahuai

    1999-01-01

    Members of the MEF2 family of transcription factors bind as homo- and heterodimers to the MEF2 site found in the promoter regions of numerous muscle-specific, growth- or stress-induced genes. We showed previously that the transactivation activity of MEF2C is stimulated by p38 mitogen-activated protein (MAP) kinase. In this study, we examined the potential role of the p38 MAP kinase pathway in regulating the other MEF2 family members. We found that MEF2A, but not MEF2B or MEF2D, is a substrate...

  18. Genome-Wide Identification and Evolutionary Analysis of the Animal Specific ETS Transcription Factor Family

    OpenAIRE

    Wang, Zhipeng; Zhang, Qin

    2009-01-01

    The ETS proteins are a family of transcription factors (TFs) that regulate a variety of biological processes. We made genome-wide analyses to explore the classification of the ETS gene family. We identified 207 ETS genes which encode 321 ETS TFs from ten animal species. Of the 321 ETS TFs, 155 contain only an ETS domain, about 50% contain a ETS_PEA3_N or a SAM_PNT domain in addition to an ETS domain, the rest (only four) contain a second ETS domain or a second ETS_PEA3_N domain or an another ...

  19. SACE_0012, a TetR-Family Transcriptional Regulator, Affects the Morphogenesis of Saccharopolyspora erythraea

    OpenAIRE

    YIN, XIAOJUAN; Xu, Xinqiang; Wu, Hang; Yuan, Li; Huang, Xunduan; Zhang, Buchang

    2013-01-01

    Saccharopolyspora erythraea, a mycelium-forming actinomycete, produces a clinically important antibiotic erythromycin. Extensive investigations have provided insights into erythromycin biosynthesis in S. erythraea, but knowledge of its morphogenesis remains limited. By gene inactivation and complementation strategies, the TetR-family transcriptional regulator SACE_0012 was identified to be a negative regulator of mycelium formation of S. erythraea A226. Detected by quantitative real-time PCR,...

  20. CRISPR families of the crenarchaeal genus Sulfolobus: bidirectional transcription and dynamic properties.

    Science.gov (United States)

    Lillestøl, Reidun K; Shah, Shiraz A; Brügger, Kim; Redder, Peter; Phan, Hien; Christiansen, Jan; Garrett, Roger A

    2009-04-01

    Clusters of regularly interspaced short palindromic repeats (CRISPRs) of Sulfolobus fall into three main families based on their repeats, leader regions, associated cas genes and putative recognition sequences on viruses and plasmids. Spacer sequence matches to different viruses and plasmids of the Sulfolobales revealed some bias particularly for family III CRISPRs. Transcription occurs on both strands of the five repeat-clusters of Sulfolobus acidocaldarius and a repeat-cluster of the conjugative plasmid pKEF9. Leader strand transcripts cover whole repeat-clusters and are processed mainly from the 3'-end, within repeats, yielding heterogeneous 40-45 nt spacer RNAs. Processing of the pKEF9 leader transcript occurred partially in spacers, and was incomplete, probably reflecting defective repeat recognition by host enzymes. A similar level of transcripts was generated from complementary strands of each chromosomal repeat-cluster and they were processed to yield discrete approximately 55 nt spacer RNAs. Analysis of the partially identical repeat-clusters of Sulfolobus solfataricus strains P1 and P2 revealed that spacer-repeat units are added upstream only when a leader and certain cas genes are linked. Downstream ends of the repeat-clusters are conserved such that deletions and recombination events occur internally.

  1. Role of the GATA family of transcription factors in endocrine development, function, and disease.

    Science.gov (United States)

    Viger, Robert S; Guittot, Séverine Mazaud; Anttonen, Mikko; Wilson, David B; Heikinheimo, Markku

    2008-04-01

    The WGATAR motif is a common nucleotide sequence found in the transcriptional regulatory regions of numerous genes. In vertebrates, these motifs are bound by one of six factors (GATA1 to GATA6) that constitute the GATA family of transcriptional regulatory proteins. Although originally considered for their roles in hematopoietic cells and the heart, GATA factors are now known to be expressed in a wide variety of tissues where they act as critical regulators of cell-specific gene expression. This includes multiple endocrine organs such as the pituitary, pancreas, adrenals, and especially the gonads. Insights into the functional roles played by GATA factors in adult organ systems have been hampered by the early embryonic lethality associated with the different Gata-null mice. This is now being overcome with the generation of tissue-specific knockout models and other knockdown strategies. These approaches, together with the increasing number of human GATA-related pathologies have greatly broadened the scope of GATA-dependent genes and, importantly, have shown that GATA action is not necessarily limited to early development. This has been particularly evident in endocrine organs where GATA factors appear to contribute to the transcription of multiple hormone-encoding genes. This review provides an overview of the GATA family of transcription factors as they relate to endocrine function and disease.

  2. Arabidopsis Ovate Family Proteins, a Novel Transcriptional Repressor Family, Control Multiple Aspects of Plant Growth and Development

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Shucai [University of British Columbia, Vancouver; Chang, Ying [Northeast Agricultural University; Guo, Jianjun [Harvard University; Zeng, Qingning [University of British Columbia, Vancouver; Ellis, Brian [University of British Columbia, Vancouver; Chen, Jay [ORNL

    2011-01-01

    BACKGROUND: The Arabidopsis genome contains 18 genes that are predicted to encode Ovate Family Proteins (AtOFPs), a protein family characterized by a conserved OVATE domain, an approximately 70-amino acid domain that was originally found in tomato OVATE protein. Among AtOFP family members, AtOFP1 has been shown to suppress cell elongation, in part, by suppressing the expression of AtGA20ox1, AtOFP4 has been shown to regulate secondary cell wall formation by interact with KNOTTED1-LIKE HOMEODOMAIN PROTEIN 7 (KNAT7), and AtOFP5 has been shown to regulate the activity of a BEL1-LIKEHOMEODOMAIN 1(BLH1)-KNAT3 complex during early embryo sac development, but little is known about the function of other AtOFPs. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated here that AtOFP proteins could function as effective transcriptional repressors in the Arabidopsis protoplast transient expression system. The analysis of loss-of-function alleles of AtOFPs suggested AtOFP genes may have overlapping function in regulating plant growth and development, because none of the single mutants identified, including T-DNA insertion mutants in AtOFP1, AtOFP4, AtOFP8, AtOFP10, AtOFP15 and AtOFP16, displayed any apparent morphological defects. Further, Atofp1 Atofp4 and Atofp15 Atofp16 double mutants still did not differ significantly from wild-type. On the other hand, plants overexpressing AtOFP genes displayed a number of abnormal phenotypes, which could be categorized into three distinct classes, suggesting that AtOFP genes may also have diverse functions in regulating plant growth and development. Further analysis suggested that AtOFP1 regulates cotyledon development in a postembryonic manner, and global transcript profiling revealed that it suppress the expression of many other genes. CONCLUSIONS/SIGNIFICANCE: Our results showed that AtOFPs function as transcriptional repressors and they regulate multiple aspects of plant growth and development. These results provided the first overview of a

  3. Analysis of functional redundancies within the Arabidopsis TCP transcription factor family.

    Science.gov (United States)

    Danisman, Selahattin; van Dijk, Aalt D J; Bimbo, Andrea; van der Wal, Froukje; Hennig, Lars; de Folter, Stefan; Angenent, Gerco C; Immink, Richard G H

    2013-12-01

    Analyses of the functions of TEOSINTE-LIKE1, CYCLOIDEA, and PROLIFERATING CELL FACTOR1 (TCP) transcription factors have been hampered by functional redundancy between its individual members. In general, putative functionally redundant genes are predicted based on sequence similarity and confirmed by genetic analysis. In the TCP family, however, identification is impeded by relatively low overall sequence similarity. In a search for functionally redundant TCP pairs that control Arabidopsis leaf development, this work performed an integrative bioinformatics analysis, combining protein sequence similarities, gene expression data, and results of pair-wise protein-protein interaction studies for the 24 members of the Arabidopsis TCP transcription factor family. For this, the work completed any lacking gene expression and protein-protein interaction data experimentally and then performed a comprehensive prediction of potential functional redundant TCP pairs. Subsequently, redundant functions could be confirmed for selected predicted TCP pairs by genetic and molecular analyses. It is demonstrated that the previously uncharacterized class I TCP19 gene plays a role in the control of leaf senescence in a redundant fashion with TCP20. Altogether, this work shows the power of combining classical genetic and molecular approaches with bioinformatics predictions to unravel functional redundancies in the TCP transcription factor family.

  4. AcEST: BP914794 [AcEST

    Lifescience Database Archive (English)

    Full Text Available se/recombinase OS=Bordete... 33 6.7 tr|Q11FQ4|Q11FQ4_MESSB Transcriptional regulator, LysR family OS... 33 8...1 RHPASTLVYGKV 402 >tr|Q11FQ4|Q11FQ4_MESSB Transcriptional regulator, LysR family

  5. NCBI nr-aa BLAST: CBRC-SARA-01-0991 [SEVENS

    Lifescience Database Archive (English)

    Full Text Available CBRC-SARA-01-0991 ref|YP_574775.1| transcriptional regulator, LysR family [Chromohalobacter salex...igens DSM 3043] gb|ABE60076.1| transcriptional regulator, LysR family [Chromohalobacter salexigens DSM 3043] YP_574775.1 9.3 31% ...

  6. HSF transcription factor family, heat shock response, and protein intrinsic disorder.

    Science.gov (United States)

    Westerheide, Sandy D; Raynes, Rachel; Powell, Chase; Xue, Bin; Uversky, Vladimir N

    2012-02-01

    Intrinsically disordered proteins are highly abundant in all kingdoms of life, and several protein functional classes, such as transcription factors, transcriptional regulators, hub and scaffold proteins, signaling proteins, and chaperones are especially enriched in intrinsic disorder. One of the unique cellular reactions to protein damaging stress is the so-called heat shock response that results in the upregulation of heat shock proteins including molecular chaperones. This molecular protective mechanism is conserved from prokaryotes to eukaryotes and allows an organism to respond to various proteotoxic stressors, such as heat shock, oxidative stress, exposure to heavy metals, and drugs. The heat shock response- related proteins can be expressed during normal conditions (e.g., during the cell growth and development) or can be induced by various pathological conditions, such as infection, inflammation, and protein conformation diseases. The initiation of the heat shock response is manifested by the activation of the heat shock transcription factors HSF 1, part of a family of related HSF transcription factors. This review analyzes the abundance and functional roles of intrinsic disorder in various heat shock transcription factors and clearly shows that the heat shock response requires HSF flexibility to be more efficient. © 2012 Bentham Science Publishers

  7. Split End Family RNA Binding Proteins: Novel Tumor Suppressors Coupling Transcriptional Regulation with RNA Processing

    Directory of Open Access Journals (Sweden)

    Hairui Su

    2015-01-01

    Full Text Available Split End (SPEN family proteins have three members: SPEN, RBM15, and RBM15B. SPEN family proteins contain three conserved RNA recognition motifs on the N-terminal region and an SPOC domain on the C-terminal region. RBM15 is fused to MKL1 in chromosome translocation t (1;22, which causes childhood acute megakaryoblastic leukemia (AMKL. Haploinsufficiency of RBM15 in AMKL indicates that RBM15 is a tumor suppressor. Both SPEN and RBM15 are mutated in a variety of cancer types, implying that they are tumor suppressors. SPEN and RBM15are required for the development of multiple organs including hematopoiesis partly via regulating the NOTCH signaling pathway, as well as the WNT signaling pathway in species ranging from Drosophila to mammals. Besides transcriptional regulation, RBM15 regulates RNA export and RNA splicing. In this review, we summarized data in the literature on how the members in SPEN family regulate gene expression at transcription and RNA processing steps. The crosstalk between epigenetic regulation and RNA metabolism is increasingly appreciated in understanding tumorigenesis. Studying the SPEN family of RNA binding proteins will create new perspectives for cancer therapy.

  8. Genome-wide identification, classification and analysis of heat shock transcription factor family in maize

    Directory of Open Access Journals (Sweden)

    Zhu Su-Wen

    2011-01-01

    Full Text Available Abstract Background Heat shock response in eukaryotes is transcriptionally regulated by conserved heat shock transcription factors (Hsfs. Hsf genes are represented by a large multigene family in plants and investigation of the Hsf gene family will serve to elucidate the mechanisms by which plants respond to stress. In recent years, reports of genome-wide structural and evolutionary analysis of the entire Hsf gene family have been generated in two model plant systems, Arabidopsis and rice. Maize, an important cereal crop, has represented a model plant for genetics and evolutionary research. Although some Hsf genes have been characterized in maize, analysis of the entire Hsf gene family were not completed following Maize (B73 Genome Sequencing Project. Results A genome-wide analysis was carried out in the present study to identify all Hsfs maize genes. Due to the availability of complete maize genome sequences, 25 nonredundant Hsf genes, named ZmHsfs were identified. Chromosomal location, protein domain and motif organization of ZmHsfs were analyzed in maize genome. The phylogenetic relationships, gene duplications and expression profiles of ZmHsf genes were also presented in this study. Twenty-five ZmHsfs were classified into three major classes (class A, B, and C according to their structural characteristics and phylogenetic comparisons, and class A was further subdivided into 10 subclasses. Moreover, phylogenetic analysis indicated that the orthologs from the three species (maize, Arabidopsis and rice were distributed in all three classes, it also revealed diverse Hsf gene family expression patterns in classes and subclasses. Chromosomal/segmental duplications played a key role in Hsf gene family expansion in maize by investigation of gene duplication events. Furthermore, the transcripts of 25 ZmHsf genes were detected in the leaves by heat shock using quantitative real-time PCR. The result demonstrated that ZmHsf genes exhibit different

  9. Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance.

    Science.gov (United States)

    Ante, Vanessa M; Bina, X Renee; Howard, Mondraya F; Sayeed, Sameera; Taylor, Dawn L; Bina, James E

    2015-11-01

    Vibrio cholerae is an aquatic organism and facultative human pathogen that colonizes the small intestine. In the small intestine, V. cholerae is exposed to a variety of antimicrobial compounds, including bile. V. cholerae resistance to bile is multifactorial and includes alterations in the membrane permeability barrier that are mediated by ToxR, a membrane-associated transcription factor. ToxR has also been shown to be required for activation of the LysR family transcription factor leuO in response to cyclic dipeptides. LeuO has been implicated in the regulation of multiple V. cholerae phenotypes, including biofilm production and virulence. In this study, we investigated the effects of bile on leuO expression. We show that leuO transcription increased in response to bile and bile salts but not in response to other detergents. The bile-dependent increase in leuO expression was dependent on ToxR, which was found to bind directly to the leuO promoter. The periplasmic domain of ToxR was required for basal leuO expression and for the bile-dependent induction of both leuO and ompU transcription. V. cholerae mutants that did not express leuO exhibited increased bile susceptibility, suggesting that LeuO contributes to bile resistance. Our collective results demonstrate that ToxR activates leuO expression in response to bile and that LeuO is a component of the ToxR-dependent responses that contribute to bile resistance. The success of Vibrio cholerae as a human pathogen is dependent upon its ability to rapidly adapt to changes in its growth environment. Growth in the human gastrointestinal tract requires the expression of genes that provide resistance to host antimicrobial compounds, including bile. In this work, we show for the first time that the LysR family regulator LeuO mediates responses in V. cholerae that contribute to bile resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  10. DMPD: The interferon-alpha/beta system in antiviral responses: a multimodal machineryof gene regulation by the IRF family of transcription factors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available ineryof gene regulation by the IRF family of transcription factors. Taniguchi T, Takaoka A. Curr Opin Immuno...sponses: a multimodal machineryof gene regulation by the IRF family of transcript...achineryof gene regulation by the IRF family of transcription factors. Authors Taniguchi T, Takaoka A. Publi

  11. Laccase Gene Family in Cerrena sp. HYB07: Sequences, Heterologous Expression and Transcriptional Analysis

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2016-08-01

    Full Text Available Laccases are a class of multi-copper oxidases with industrial potential. In this study, eight laccases (Lac1–8 from Cerrena sp. strain HYB07, a white-rot fungus with high laccase yields, were analyzed. The laccases showed moderate identities to each other as well as with other fungal laccases and were predicted to have high redox potentials except for Lac6. Selected laccase isozymes were heterologously expressed in the yeast Pichia pastoris, and different enzymatic properties were observed. Transcription of the eight laccase genes was differentially regulated during submerged and solid state fermentation, as shown by quantitative real-time polymerase chain reaction and validated reference genes. During 6-day submerged fermentation, Lac7 and 2 were successively the predominantly expressed laccase gene, accounting for over 95% of all laccase transcripts. Interestingly, accompanying Lac7 downregulation, Lac2 transcription was drastically upregulated on days 3 and 5 to 9958-fold of the level on day 1. Consistent with high mRNA abundance, Lac2 and 7, but not other laccases, were identified in the fermentation broth by LC-MS/MS. In solid state fermentation, less dramatic differences in transcript abundance were observed, and Lac3, 7 and 8 were more highly expressed than other laccase genes. Elucidating the properties and expression profiles of the laccase gene family will facilitate understanding, production and commercialization of the fungal strain and its laccases.

  12. The Function of the MEF2 Family of Transcription Factors in Cardiac Development, Cardiogenomics, and Direct Reprogramming

    Directory of Open Access Journals (Sweden)

    Cody A. Desjardins

    2016-08-01

    Full Text Available Proper formation of the mammalian heart requires precise spatiotemporal transcriptional regulation of gene programs in cardiomyocytes. Sophisticated regulatory networks have evolved to not only integrate the activities of distinct transcription factors to control tissue-specific gene programs but also, in many instances, to incorporate multiple members within these transcription factor families to ensure accuracy and specificity in the system. Unsurprisingly, perturbations in this elaborate transcriptional circuitry can lead to severe cardiac abnormalities. Myocyte enhancer factor–2 (MEF2 transcription factor belongs to the evolutionarily conserved cardiac gene regulatory network. Given its central role in muscle gene regulation and its evolutionary conservation, MEF2 is considered one of only a few core cardiac transcription factors. In addition to its firmly established role as a differentiation factor, MEF2 regulates wide variety of, sometimes antagonistic, cellular processes such as cell survival and death. Vertebrate genomes encode multiple MEF2 family members thereby expanding the transcriptional potential of this core transcription factor in the heart. This review highlights the requirement of the MEF2 family and their orthologs in cardiac development in diverse animal model systems. Furthermore, we describe the recently characterized role of MEF2 in direct reprogramming and genome-wide cardiomyocyte gene regulation. A thorough understanding of the regulatory functions of the MEF2 family in cardiac development and cardiogenomics is required in order to develop effective therapeutic strategies to repair the diseased heart.

  13. Local gene regulation details a recognition code within the LacI transcriptional factor family.

    Directory of Open Access Journals (Sweden)

    Francisco M Camas

    Full Text Available The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs and nucleotides (NTs. This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs. We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations--determined by two AAs of the TFs and two NTs in the binding sites--that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications.

  14. The Fos family of transcription factors and their role in tumourigenesis.

    Science.gov (United States)

    Milde-Langosch, Karin

    2005-11-01

    Members of the Fos family (c-Fos, FosB and its smaller splice variants, Fra-1 and Fra-2) dimerise with Jun proteins to form the AP-1 transcription factor complex. Based on the rapidly growing amount of data from experimental studies, animal models and investigations on clinical tumour samples, this review summarises the current knowledge about the role of these proteins in carcinogenesis. In addition to c-Fos, which has oncogenic activity and is frequently overexpressed in tumour cells, Fra-1 seems to play a role in the progression of many carcinomas. The results obtained from various studies show different implications for these transcription factors according to tumour type, i.e., Fra-1 overexpression enhances the motility and invasion of breast and colorectal cancer cells, but inhibits the tumourigenicity of cervical carcinoma cell lines. Knowledge about regulation of invasion and metastasis in different malignant tumours in vivo might open promising perspectives to targeted therapeutic approaches.

  15. Genome-Wide Analysis and Molecular Characterization of Heat Shock Transcription Factor Family in Glycine max

    Institute of Scientific and Technical Information of China (English)

    Eunsook Chung; Kyoung-Mi Kim; Jai-Heon Lee

    2013-01-01

    Heat shock transcription factors (Hsfs) play an essential role on the increased tolerance against heat stress by regulating the expression of heat-responsive genes.In this study,a genome-wide analysis was performed to identify all of the soybean (Glycine max) GmHsfgenes based on the latest soybean genome sequence.Chromosomal location,protein domain,motif organization,and phylogenetic relationships of 26 non-redundant GmHsf genes were analyzed compared with AtHsfs (Arabidopsis thaliana Hsfs).According to their structural features,the predicted members were divided into the previously defined classes A-C,as described for AtHsfs.Transcript levels and subcellular localization of five GmHsfs responsive to abiotic stresses were analyzed by real-time RT-PCR.These results provide a fundamental clue for understanding the complexity of the soybean GmHsfgene family and cloning the functional genes in future studies.

  16. Functional conservation between members of an ancient duplicated transcription factor family, LSF/Grainyhead.

    Science.gov (United States)

    Venkatesan, Kavitha; McManus, Heather R; Mello, Craig C; Smith, Temple F; Hansen, Ulla

    2003-08-01

    The LSF/Grainyhead transcription factor family is involved in many important biological processes, including cell cycle, cell growth and development. In order to investigate the evolutionary conservation of these biological roles, we have characterized two new family members in Caenorhabditis elegans and Xenopus laevis. The C.elegans member, Ce-GRH-1, groups with the Grainyhead subfamily, while the X.laevis member, Xl-LSF, groups with the LSF subfamily. Ce-GRH-1 binds DNA in a sequence-specific manner identical to that of Drosophila melanogaster Grainyhead. In addition, Ce-GRH-1 binds to sequences upstream of the C.elegans gene encoding aromatic L-amino-acid decarboxylase and genes involved in post-embryonic development, mab-5 and dbl-1. All three C.elegans genes are homologs of D.melanogaster Grainyhead-regulated genes. RNA-mediated interference of Ce-grh-1 results in embryonic lethality in worms, accompanied by soft, defective cuticles. These phenotypes are strikingly similar to those observed previously in D.melanogaster grainyhead mutants, suggesting conservation of the developmental role of these family members over the course of evolution. Our phylogenetic analysis of the expanded LSF/GRH family (including other previously unrecognized proteins/ESTs) suggests that the structural and functional dichotomy of this family dates back more than 700 million years, i.e. to the time when the first multicellular organisms are thought to have arisen.

  17. The Role of the E2F Transcription Factor Family in UV-Induced Apoptosis

    Directory of Open Access Journals (Sweden)

    Orla Gannon

    2011-12-01

    Full Text Available The E2F transcription factor family is traditionally associated with cell cycle control. However, recent data has shown that activating E2Fs (E2F1-3a are potent activators of apoptosis. In contrast, the recently cloned inhibitory E2Fs (E2F7 and 8 appear to antagonize E2F-induced cell death. In this review we will discuss (i the potential role of E2Fs in UV-induced cell death and (ii the implications of this to the development of UV-induced cutaneous malignancies.

  18. Identification of the transcriptional activator controlling the butanediol fermentation pathway in Klebsiella terrigena.

    Science.gov (United States)

    Mayer, D; Schlensog, V; Böck, A

    1995-09-01

    The gene budR, whose product is responsible for induction of the butanediol formation pathway under fermentative growth conditions in Klebsiella terrigena, has been cloned and sequenced. This gene is separated from the budABC operon by a nontranslated region of 106 bp and transcribed in the opposite direction. budR codes for a protein of molecular weight 32,124, the sequence of which exhibits characteristics of regulators belonging to the LysR family. When transferred into the heterologous host Escherichia coli, budR activates expression of budA'-lacZ transcriptional and translational fusions with a regulatory pattern identical to that in K. terrigena, namely, induction by acetate, low pH, and anaerobiosis. Induction by acetate was specific, indicating that it is the physiological inducer. Primer extension analysis located the start site of transcription to two positions, 23 and 24 bp upstream of the budR initiation codon, and also showed that BudR strongly autoregulates its own expression. The products of fhlA, arcA, hip, ntrA, and katF did not influence expression of the bud operon. A mutation in fnr, however, led to a threefold increase in expression, indicating that Fnr acts as a repressor. The results support the notion that BudR coordinates the activity of the energy-conserving, nonreductive, but acidifying acetate formation pathway with the expression of the non-energy-conserving, reductive, but nonacidifying butanediol pathway.

  19. Overrepresentation of transcription factor families in the genesets underlying breast cancer subtypes

    Directory of Open Access Journals (Sweden)

    Joshi Himanshu

    2012-05-01

    Full Text Available Abstract Background The human genome contains a large amount of cis-regulatory DNA elements responsible for directing both spatial and temporal gene-expression patterns. Previous studies have shown that based on their mRNA expression breast tumors could be divided into five subgroups (Luminal A, Luminal B, Basal, ErbB2+ and Normal-like, each with a distinct molecular portrait. Whole genome gene expression analysis of independent sets of breast tumors reveals repeatedly the robustness of this classification. Furthermore, breast tumors carrying a TP53 mutation show a distinct gene expression profile, which is in strong association to the distinct molecular portraits. The mRNA expression of 552 genes, which varied considerably among the different tumors, but little between two samples of the same tumor, has been shown to be sufficient to separate these tumor subgroups. Results We analyzed in silico the transcriptional regulation of genes defining the subgroups at 3 different levels: 1. We studied the pathways in which the genes distinguishing the subgroups of breast cancer may be jointly involved including upstream regulators (1st and 2nd level of regulation as well as downstream targets of these genes. 2. Then we analyzed the promoter areas of these genes (−500 bp tp +100 bp relative to the transcription start site for canonical transcription binding sites using Genomatix. 3. We looked for the actual expression levels of the identified TF and how they correlate with the overrepresentation of their TF binding sites in the separate groups. We report that promoter composition of the genes that most strongly predict the patient subgroups is distinct. The class-predictive genes showed a clearly different degree of overrepresentation of transcription factor families in their promoter sequences. Conclusion The study suggests that transcription factors responsible for the observed expression pattern in breast cancers may lead us to important biological

  20. A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead.

    Science.gov (United States)

    Wilanowski, Tomasz; Tuckfield, Annabel; Cerruti, Loretta; O'Connell, Sinead; Saint, Robert; Parekh, Vishwas; Tao, Jianning; Cunningham, John M; Jane, Stephen M

    2002-06-01

    The Drosophila transcription factor Grainyhead regulates several key developmental processes. Three mammalian genes, CP2, LBP-1a and LBP-9 have been previously identified as homologues of grainyhead. We now report the cloning of two new mammalian genes (Mammalian grainyhead (MGR) and Brother-of-MGR (BOM)) and one new Drosophila gene (dCP2) that rewrite the phylogeny of this family. We demonstrate that MGR and BOM are more closely related to grh, whereas CP2, LBP-1a and LBP-9 are descendants of the dCP2 gene. MGR shares the greatest sequence homology with grh, is expressed in tissue-restricted patterns more comparable to grh and binds to and transactivates the promoter of the human Engrailed-1 gene, the mammalian homologue of the key grainyhead target gene, engrailed. This sequence and functional conservation indicates that the new mammalian members of this family play important developmental roles.

  1. GATA family of transcription factors of vertebrates: phylogenetics and chromosomal synteny

    Indian Academy of Sciences (India)

    Chunjiang He; Hanhua Cheng; Rongjia Zhou

    2007-12-01

    GATA genes are an evolutionarily conserved family, which encode a group of important transcription factors involved in the regulation of diverse processes including the development of the heart, haematopoietic system and sex gonads. However, the evolutionary history of the GATA family has not been completely understood. We constructed a complete phylogenetic tree with functional domain information of the GATA genes of both vertebrates and several invertebrates, and mapped the GATA genes onto relevant chromosomes. Conserved synteny was observed around the GATA loci on the chromosomes. GATAs have a tendency to segregate onto different chromosomes during evolution. The phylogenetic tree is consistent with the relevant functions of GATA members. Analysis of the zinc finger domain showed that the domain tends to be duplicated during evolution from invertebrates to vertebrates. We propose that the balance between duplications of zinc finger domains and GATA members should be maintained to exert their physiological roles in each evolutionary stage. Therefore, evolutionary pressure on the GATAs must exist to maintain the balance during evolution from invertebrates to vertebrates. These results reveal the evolutionary characteristics of the GATA family and contribute to a better understanding of the relationship between evolution and biological functions of the gene family, which will help to uncover the GATAs’ biological roles, evolution and their relationship with associated diseases.

  2. Comprehensive analysis of the homeodomain-leucine zipper IV transcription factor family in Cucumis sativus.

    Science.gov (United States)

    Fu, Rao; Liu, Wei; Li, Qiang; Li, Jing; Wang, Lina; Ren, Zhonghai

    2013-07-01

    The class IV homeodomain-leucine zipper (HD-Zip IV) proteins are plant-specific transcriptional factors known to play crucial roles in plant growth and development. In this study, 11 cucumber (Cucumis sativus) HD-Zip IV genes were identified in the version 2 cucumber genome and found to be distributed unevenly across the chromosomes. The CsHDZIV (Cucumis sativus homeodomain-leucine zipper IV) gene family is smaller than in other studied species (except for rice) because of the absence of gene duplication events. Phylogenetic analysis showed that HD-Zip IV genes from cucumber, Arabidopsis, tomato, cotton, maize, and rice could be classified into five subgroups. All CsHDZIV genes appear to be derived from a basic module containing 11 exons in the coding region. Two conserved motifs of 21 and 19 nucleotides were found in the 3'-untranslated regions of six CsHDZIV genes, suggesting that post-transcriptional regulation may play a role in regulation of CsHDZIV genes. In addition, 6 of 11 CsHDZIV genes were found to undergo alternative splicing events. Reverse transcription PCR analysis showed that all CsHDZIV genes (except one) were expressed and showed preferential expression in reproductive organs.

  3. Transcriptional activation capacity of the novel PLAG family of zinc finger proteins.

    Science.gov (United States)

    Kas, K; Voz, M L; Hensen, K; Meyen, E; Van de Ven, W J

    1998-09-04

    We have isolated and characterized two novel cDNAs encoding C2H2 zinc finger proteins showing high sequence homology to PLAG1, a protein ectopically activated by promoter swapping or promoter substitution in pleomorphic adenomas with chromosomal abnormalities at chromosome 8q12. PLAG1 and the two new PLAG1 family members (PLAGL1 and PLAGL2) constitute a novel subfamily of zinc finger proteins that recognize DNA and/or RNA. To examine the potential of the three human proteins to modulate transcription, we constructed several PLAG/GAL4 DNA binding domain fusion proteins and measured their ability to activate transcription of a reporter gene construct in different mammalian cell lines and in yeast. Although the carboxyl-terminal part of PLAGL1 shows strong overall transcriptional activity in mesenchymal (COS-1) and epithelial cells (293), both PLAG1 and PLAGL2 transactivate in mesenchymal cells only if depleted from a repressing region. This effect is less profound in epithelial cells. These data suggest that the activation in pleomorphic adenomas of PLAG1 most likely results in uncontrolled activation of downstream target genes.

  4. Coactivator-dependent acetylation stabilizes members of the SREBP family of transcription factors.

    Science.gov (United States)

    Giandomenico, Valeria; Simonsson, Maria; Grönroos, Eva; Ericsson, Johan

    2003-04-01

    Members of the SREBP family of transcription factors control cholesterol and lipid homeostasis and play important roles during adipocyte differentiation. The transcriptional activity of SREBPs is dependent on the coactivators p300 and CBP. We now present evidence that SREBPs are acetylated by the intrinsic acetyltransferase activity of p300 and CBP. In SREBP1a, the acetylated lysine residue resides in the DNA-binding domain of the protein. Coexpression with p300 dramatically increases the expression of both SREBP1a and SREBP2, and this effect is dependent on the acetyltransferase activity of p300, indicating that acetylation of SREBPs regulates their stability. Indeed, acetylation or mutation of the acetylated lysine residue in SREBP1a stabilizes the protein. We demonstrate that the acetylated residue in SREBP1a is also targeted by ubiquitination and that acetylation inhibits this process. Thus, our studies define acetylation-dependent stabilization of transcription factors as a novel mechanism for coactivators to regulate gene expression.

  5. Transcriptional Activity of Nuclear Factor κB Family Genes in Patients with Systemic Sclerosis.

    Science.gov (United States)

    Lis-Święty, Anna; Gola, Joanna; Mazurek, Urszula; Brzezińska-Wcisło, Ligia

    2017-05-01

    Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology and unclear pathogenesis. Evaluation of the activation of nuclear factor κB (NF-κB) family genes IκBα, p50, p52, p65, and c-Rel, potentially involved in the regulation of immunity, inflammation, angiogenesis, and tissue remodeling in SSc, was carried out. The study included 19 patients with limited SSc, 11 patients with early SSc, and 10 healthy persons constituting the control group. Real-time QRT-PCR was used to evaluate the mRNAs in peripheral blood samples. The patients with early SSc showed a decrease in transcriptional activity of IκBα inhibitor and c-Rel subunit. Transcriptional activity decrease in the other patients with limited SSc included genes encoding c-Rel and p50, subunits of NF-κB factor. Deregulation of intracellular signal transduction by NF-κB takes place at the beginning of SSc and in its fibrosis stage. Associations between clinical variables and NF-κB related gene expression as well as the activation of NF-κB family members in SSc patients should be addressed in future studies. © 2017 by the Association of Clinical Scientists, Inc.

  6. Genomewide analysis of TCP transcription factor gene family in Malus domestica

    Indian Academy of Sciences (India)

    Ruirui Xu; Peng Sun; Fengjuan Jia; Longtao Lu; Yuanyuan Li; Shizhong Zhang; Jinguang Huang

    2014-12-01

    Teosinte branched1/cycloidea/proliferating cell factor1 (TCP) proteins are a large family of transcriptional regulators in angiosperms. They are involved in various biological processes, including development and plant metabolism pathways. In this study, a total of 52 TCP genes were identified in apple (Malus domestica) genome. Bioinformatic methods were employed to predicate and analyse their relevant gene classification, gene structure, chromosome location, sequence alignment and conserved domains of MdTCP proteins. Expression analysis from microarray data showed that the expression levels of 28 and 51 MdTCP genes changed during the ripening and rootstock–scion interaction processes, respectively. The expression patterns of 12 selected MdTCP genes were analysed in different tissues and in response to abiotic stresses. All of the selected genes were detected in at least one of the tissues tested, and most of them were modulated by adverse treatments indicating that the MdTCPs were involved in various developmental and physiological processes. To the best of our knowledge, this is the first study of a genomewide analysis of apple TCP gene family. These results provide valuable information for studies on functions of the TCP transcription factor genes in apple.

  7. Differential expression of members of the E2F family of transcription factors in rodent testes

    Directory of Open Access Journals (Sweden)

    Toppari Jorma

    2006-12-01

    Full Text Available Abstract Background The E2F family of transcription factors is required for the activation or repression of differentially expressed gene programs during the cell cycle in normal and abnormal development of tissues. We previously determined that members of the retinoblastoma protein family that interacts with the E2F family are differentially expressed and localized in almost all the different cell types and tissues of the testis and in response to known endocrine disruptors. In this study, the cell-specific and stage-specific expression of members of the E2F proteins has been elucidated. Methods We used immunohistochemical (IHC analysis of tissue sections and Western blot analysis of proteins, from whole testis and microdissected stages of seminiferous tubules to study the differential expression of the E2F proteins. Results For most of the five E2F family members studied, the localizations appear conserved in the two most commonly studied rodent models, mice and rats, with some notable differences. Comparisons between wild type and E2F-1 knockout mice revealed that the level of E2F-1 protein is stage-specific and most abundant in leptotene to early pachytene spermatocytes of stages IX to XI of mouse while strong staining of E2F-1 in some cells close to the basal lamina of rat tubules suggest that it may also be expressed in undifferentiated spermatogonia. The age-dependent development of a Sertoli-cell-only phenotype in seminiferous tubules of E2F-1 knockout males corroborates this, and indicates that E2F-1 is required for spermatogonial stem cell renewal. Interestingly, E2F-3 appears in both terminally differentiated Sertoli cells, as well as spermatogonial cells in the differentiative pathway, while the remaining member of the activating E2Fs, E2F-2 is most concentrated in spermatocytes of mid to late prophase of meiosis. Comparisons between wildtype and E2F-4 knockout mice demonstrated that the level of E2F-4 protein displays a distinct

  8. DDX11L: a novel transcript family emerging from human subtelomeric regions

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    D'Urso Michele

    2009-05-01

    Full Text Available Abstract Background The subtelomeric regions of human chromosomes exhibit an extraordinary plasticity. To date, due to the high GC content and to the presence of telomeric repeats, the subtelomeric sequences are underrepresented in the genomic libraries and consequently their sequences are incomplete in the finished human genome sequence, and still much remains to be learned about subtelomere organization, evolution and function. Indeed, only in recent years, several studies have disclosed, within human subtelomeres, novel gene family members. Results During a project aimed to analyze genes located in the telomeric region of the long arm of the human X chromosome, we have identified a novel transcript family, DDX11L, members of which map to 1pter, 2q13/14.1, 2qter, 3qter, 6pter, 9pter/9qter, 11pter, 12pter, 15qter, 16pter, 17pter, 19pter, 20pter/20qter, Xpter/Xqter and Yqter. Furthermore, we partially sequenced the underrepresented subtelomeres of human chromosomes showing a common evolutionary origin. Conclusion Our data indicate that an ancestral gene, originated as a rearranged portion of the primate DDX11 gene, and propagated along many subtelomeric locations, is emerging within subtelomeres of human chromosomes, defining a novel gene family. These findings support the possibility that the high plasticity of these regions, sites of DNA exchange among different chromosomes, could trigger the emergence of new genes.

  9. Arbuscular mycorrhiza Symbiosis Induces a Major Transcriptional Reprogramming of the Potato SWEET Sugar Transporter Family.

    Science.gov (United States)

    Manck-Götzenberger, Jasmin; Requena, Natalia

    2016-01-01

    Biotrophic microbes feeding on plants must obtain carbon from their hosts without killing the cells. The symbiotic Arbuscular mycorrhizal (AM) fungi colonizing plant roots do so by inducing major transcriptional changes in the host that ultimately also reprogram the whole carbon partitioning of the plant. AM fungi obtain carbohydrates from the root cortex apoplast, in particular from the periarbuscular space that surrounds arbuscules. However, the mechanisms by which cortical cells export sugars into the apoplast for fungal nutrition are unknown. Recently a novel type of sugar transporter, the SWEET, able to perform not only uptake but also efflux from cells was identified. Plant SWEETs have been shown to be involved in the feeding of pathogenic microbes and are, therefore, good candidates to play a similar role in symbiotic associations. Here we have carried out the first phylogenetic and expression analyses of the potato SWEET family and investigated its role during mycorrhiza symbiosis. The potato genome contains 35 SWEETs that cluster into the same four clades defined in Arabidopsis. Colonization of potato roots by the AM fungus Rhizophagus irregularis imposes major transcriptional rewiring of the SWEET family involving, only in roots, changes in 22 of the 35 members. None of the SWEETs showed mycorrhiza-exclusive induction and most of the 12 induced genes belong to the putative hexose transporters of clade I and II, while only two are putative sucrose transporters from clade III. In contrast, most of the repressed transcripts (10) corresponded to clade III SWEETs. Promoter-reporter assays for three of the induced genes, each from one cluster, showed re-localization of expression to arbuscule-containing cells, supporting a role for SWEETs in the supply of sugars at biotrophic interfaces. The complex transcriptional regulation of SWEETs in roots in response to AM fungal colonization supports a model in which symplastic sucrose in cortical cells could be cleaved

  10. Arbuscular mycorrhiza symbiosis induces a major transcriptional reprogramming of the potato SWEET sugar transporter family

    Directory of Open Access Journals (Sweden)

    Jasmin eManck-Götzenberger

    2016-04-01

    Full Text Available Biotrophic microbes feeding on plants must obtain carbon from their hosts without killing the cells. The symbiotic arbuscular mycorrhizal (AM fungi colonizing plant roots do so by inducing major transcriptional changes in the host that ultimately also reprogram the whole carbon partitioning of the plant. AM fungi obtain carbohydrates from the root cortex apoplast, in particular from the periarbuscular space that surrounds arbuscules. However, the mechanisms by which cortical cells export sugars into the apoplast for fungal nutrition are unknown. Recently a novel type of sugar transporter, the SWEET, able to perform not only uptake but also efflux from cells was identified. Plant SWEETs have been shown to be involved in the feeding of pathogenic microbes and are, therefore, good candidates to play a similar role in symbiotic associations. Here we have carried out the first phylogenetic and expression analyses of the potato SWEET family and investigated its role during mycorrhiza symbiosis. The potato genome contains 35 SWEETs that cluster into the same four clades defined in Arabidopsis. Colonization of potato roots by the AM fungus Rhizophagus irregularis imposes major transcriptional rewiring of the SWEET family involving, only in roots, changes in 22 of the 35 members. None of the SWEETs showed mycorrhiza-exclusive induction and most of the twelve induced genes belong to the putative hexose transporters of clade I and II, while only two are putative sucrose transporters from clade III. In contrast, most of the repressed transcripts (10 corresponded to clade III SWEETs. Promoter-reporter assays for three of the induced genes, each from one cluster, showed re-localization of expression to arbuscule-containing cells, supporting a role for SWEETs in the supply of sugars at biotrophic interfaces. The complex transcriptional regulation of SWEETs in roots in response to AM fungal colonization supports a model in which symplastic sucrose in cortical

  11. A Single Gene Target of an ETS-Family Transcription Factor Determines Neuronal CO2-Chemosensitivity

    Science.gov (United States)

    Brandt, Julia P.; Martinez-Velazquez, Luis A.; Petersen, Jakob Gramstrup; Pocock, Roger; Ringstad, Niels

    2012-01-01

    Many animals possess neurons specialized for the detection of carbon dioxide (CO2), which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO2. The ETS-5 transcription factor is necessary for the specification of CO2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO2-detection and transforms neurons into CO2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO2-sensing neurons in other phyla. PMID:22479504

  12. Functions and Application of the AP2/ERF Transcription Factor Family in Crop Improvement

    Institute of Scientific and Technical Information of China (English)

    Zhao-Shi Xu; Ming Chen; Lian-Cheng Li; You-Zhi Ma

    2011-01-01

    Plants have acquired sophisticated stress response systems to adapt to changing environments. It is important to understand plants' stress response mechanisms in the effort to improve crop productivity under stressful conditions. The AP2/ERF transcription factors are known to regulate diverse processes of plant development and stress responses.In this study, the molecular characteristics and biological functions of AP2/ERFs in a variety of plant species were analyzed. AP2/ERFs,especially those in DREB and ERF subfamilies, are ideal candidates for crop improvement because their overexpression enhances tolerances to drought, salt, freezing, as well as resistances to multiple diseases in the transgenic plants. The comprehensive analysis of physiological functions is useful in elucidating the biological roles of AP2/ERF family genes in gene interaction, pathway regulation, and defense response under stress environments, which should provide new opportunities for the crop tolerance engineering.

  13. A single gene target of an ETS-family transcription factor determines neuronal CO2-chemosensitivity.

    Directory of Open Access Journals (Sweden)

    Julia P Brandt

    Full Text Available Many animals possess neurons specialized for the detection of carbon dioxide (CO(2, which acts as a cue to elicit behavioral responses and is also an internally generated product of respiration that regulates animal physiology. In many organisms how such neurons detect CO(2 is poorly understood. We report here a mechanism that endows C. elegans neurons with the ability to detect CO(2. The ETS-5 transcription factor is necessary for the specification of CO(2-sensing BAG neurons. Expression of a single ETS-5 target gene, gcy-9, which encodes a receptor-type guanylate cyclase, is sufficient to bypass a requirement for ets-5 in CO(2-detection and transforms neurons into CO(2-sensing neurons. Because ETS-5 and GCY-9 are members of gene families that are conserved between nematodes and vertebrates, a similar mechanism might act in the specification of CO(2-sensing neurons in other phyla.

  14. Genome-wide classification and expression analysis of MYB transcription factor families in rice and Arabidopsis

    Directory of Open Access Journals (Sweden)

    Katiyar Amit

    2012-10-01

    Full Text Available Abstract Background The MYB gene family comprises one of the richest groups of transcription factors in plants. Plant MYB proteins are characterized by a highly conserved MYB DNA-binding domain. MYB proteins are classified into four major groups namely, 1R-MYB, 2R-MYB, 3R-MYB and 4R-MYB based on the number and position of MYB repeats. MYB transcription factors are involved in plant development, secondary metabolism, hormone signal transduction, disease resistance and abiotic stress tolerance. A comparative analysis of MYB family genes in rice and Arabidopsis will help reveal the evolution and function of MYB genes in plants. Results A genome-wide analysis identified at least 155 and 197 MYB genes in rice and Arabidopsis, respectively. Gene structure analysis revealed that MYB family genes possess relatively more number of introns in the middle as compared with C- and N-terminal regions of the predicted genes. Intronless MYB-genes are highly conserved both in rice and Arabidopsis. MYB genes encoding R2R3 repeat MYB proteins retained conserved gene structure with three exons and two introns, whereas genes encoding R1R2R3 repeat containing proteins consist of six exons and five introns. The splicing pattern is similar among R1R2R3 MYB genes in Arabidopsis. In contrast, variation in splicing pattern was observed among R1R2R3 MYB members of rice. Consensus motif analysis of 1kb upstream region (5′ to translation initiation codon of MYB gene ORFs led to the identification of conserved and over-represented cis-motifs in both rice and Arabidopsis. Real-time quantitative RT-PCR analysis showed that several members of MYBs are up-regulated by various abiotic stresses both in rice and Arabidopsis. Conclusion A comprehensive genome-wide analysis of chromosomal distribution, tandem repeats and phylogenetic relationship of MYB family genes in rice and Arabidopsis suggested their evolution via duplication. Genome-wide comparative analysis of MYB genes and

  15. 1Novel MEFV transcripts in Familial Mediterranean fever patients and controls

    Directory of Open Access Journals (Sweden)

    Jalkh Nadine

    2010-06-01

    Full Text Available Abstract Background Familial Mediterranean fever is a recessive autoinflammatory disease frequently encountered in Armenians, Jews, Arabs and Turks. The MEFV gene is responsible for the disease. It encodes a protein called pyrin/marenostrin involved in the innate immune system. A large number of clinically diagnosed FMF patients carry only one MEFV mutation. This study aims at studying the MEFV gene splicing pattern in heterozygous FMF patients and healthy individuals, in an attempt to understand the mechanism underlying the disease in these patients. Methods RNA was extracted from peripheral blood leucocytes of 41 FMF patients and 34 healthy individuals. RT-PCR was then performed, and the amplified products were migrated on a polyacrylamide electrophoresis gel, characterized by gel extraction of the corresponding bands followed by sequencing. Results Five novel splicing events were observed in both patients and controls deleting either exons 3, 4 (del34, or exons 2, 3, 4 (del234, or exons 2, 3, 4, 5 (del2345 or exon7 (del7 or exons 7 and 8 (del78. Conclusions The observation of such qualitative variability in the expression of the MEFV gene suggests a complex transcriptional regulation. However, the expression of these novel transcripts in both patients and controls is not in favour of a severe pathogenic effect.

  16. A Model for Dimerization of the SOX Group E Transcription Factor Family.

    Science.gov (United States)

    Ramsook, Sarah N; Ni, Joyce; Shahangian, Shokofeh; Vakiloroayaei, Ana; Khan, Naveen; Kwan, Jamie J; Donaldson, Logan W

    2016-01-01

    Group E members of the SOX transcription factor family include SOX8, SOX9, and SOX10. Preceding the high mobility group (HMG) domain in each of these proteins is a thirty-eight amino acid region that supports the formation of dimers on promoters containing tandemly inverted sites. The purpose of this study was to obtain new structural insights into how the dimerization region functions with the HMG domain. From a mutagenic scan of the dimerization region, the most essential amino acids of the dimerization region were clustered on the hydrophobic face of a single, predicted amphipathic helix. Consistent with our hypothesis that the dimerization region directly contacts the HMG domain, a peptide corresponding to the dimerization region bound a preassembled HMG-DNA complex. Sequence conservation among Group E members served as a basis to identify two surface exposed amino acids in the HMG domain of SOX9 that were necessary for dimerization. These data were combined to make a molecular model that places the dimerization region of one SOX9 protein onto the HMG domain of another SOX9 protein situated at the opposing site of a tandem promoter. The model provides a detailed foundation for assessing the impact of mutations on SOX Group E transcription factors.

  17. The WRKY Transcription Factor Family in Citrus: Valuable and Useful Candidate Genes for Citrus Breeding.

    Science.gov (United States)

    Ayadi, M; Hanana, M; Kharrat, N; Merchaoui, H; Marzoug, R Ben; Lauvergeat, V; Rebaï, A; Mzid, R

    2016-10-01

    WRKY transcription factors belong to a large family of plant transcriptional regulators whose members have been reported to be involved in a wide range of biological roles including plant development, adaptation to environmental constraints and response to several diseases. However, little or poor information is available about WRKY's in Citrus. The recent release of completely assembled genomes sequences of Citrus sinensis and Citrus clementina and the availability of ESTs sequences from other citrus species allowed us to perform a genome survey for Citrus WRKY proteins. In the present study, we identified 100 WRKY members from C. sinensis (51), C. clementina (48) and Citrus unshiu (1), and analyzed their chromosomal distribution, gene structure, gene duplication, syntenic relation and phylogenetic analysis. A phylogenetic tree of 100 Citrus WRKY sequences with their orthologs from Arabidopsis has distinguished seven groups. The CsWRKY genes were distributed across all ten sweet orange chromosomes. A comprehensive approach and an integrative analysis of Citrus WRKY gene expression revealed variable profiles of expression within tissues and stress conditions indicating functional diversification. Thus, candidate Citrus WRKY genes have been proposed as potentially involved in fruit acidification, essential oil biosynthesis and abiotic/biotic stress tolerance. Our results provided essential prerequisites for further WRKY genes cloning and functional analysis with an aim of citrus crop improvement.

  18. Transcriptional regulator LsrB of Sinorhizobium meliloti positively regulates the expression of genes involved in lipopolysaccharide biosynthesis.

    Science.gov (United States)

    Tang, Guirong; Wang, Ying; Luo, Li

    2014-09-01

    Rhizobia induce nitrogen-fixing nodules on host legumes, which is important in agriculture and ecology. Lipopolysaccharide (LPS) produced by rhizobia is required for infection or bacteroid survival in host cells. Genes required for LPS biosynthesis have been identified in several Rhizobium species. However, the regulation of their expression is not well understood. Here, Sinorhizobium meliloti LsrB, a member of the LysR family of transcriptional regulators, was found to be involved in LPS biosynthesis by positively regulating the expression of the lrp3-lpsCDE operon. An lsrB in-frame deletion mutant displayed growth deficiency, sensitivity to the detergent sodium dodecyl sulfate, and acidic pH compared to the parent strain. This mutant produced slightly less LPS due to lower expression of the lrp3 operon. Analysis of the transcriptional start sites of the lrp3 and lpsCDE gene suggested that they constitute one operon. The expression of lsrB was positively autoregulated. The promoter region of lrp3 was specifically precipitated by anti-LsrB antibodies in vivo. The promoter DNA fragment containing TN11A motifs was bound by the purified LsrB protein in vitro. These new findings suggest that S. meliloti LsrB is associated with LPS biosynthesis, which is required for symbiotic nitrogen fixation on some ecotypes of alfalfa plants.

  19. Differential transcription of the major antigenic protein 1 multigene family of Ehrlichia ruminantium in Amblyomma variegatum ticks.

    Science.gov (United States)

    Postigo, M; Taoufik, A; Bell-Sakyi, L; de Vries, E; Morrison, W I; Jongejan, F

    2007-06-21

    The rickettsial pathogen Ehrlichia ruminantium causes heartwater in ruminants and is transmitted by ticks of the genus Amblyomma. The map1 gene, encoding the major surface protein MAP1, is a member of a multigene family containing 16 paralogs. In order to investigate differential transcription of genes of the map1 multigene family in vivo in unfed and feeding ticks, RNA was extracted from midguts and salivary glands of E. ruminantium-infected adult female Amblyomma variegatum ticks and analysed by RT-PCR using MAP1 paralog-specific primers. In unfed ticks, only transcripts from the map1-1 gene were observed in midguts and no transcripts were detected in salivary glands. In feeding ticks, map1-1 transcripts were more abundant in midguts whereas high levels of map1 transcripts were observed in salivary glands. Our results show that differential transcription of genes of the E. ruminantium map1 cluster occurs in vivo in different tissues of infected ticks before and during transmission feeding, indicating that this multigene family may be involved in functions of biological relevance in different stages of the life cycle of E. ruminantium.

  20. TCPs, WUSs, and WINDs: families of transcription factors that regulate shoot meristem formation, stem cell maintenance, and somatic cell differentiation.

    Science.gov (United States)

    Ikeda, Miho; Ohme-Takagi, Masaru

    2014-01-01

    In contrast to somatic mammalian cells, which cannot alter their fate, plant cells can dedifferentiate to form totipotent callus cells and regenerate a whole plant, following treatment with specific phytohormones. However, the regulatory mechanisms and key factors that control differentiation-dedifferentiation and cell totipotency have not been completely clarified in plants. Recently, several plant transcription factors that regulate meristem formation and dedifferentiation have been identified and include members of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP), WUSCHEL (WUS), and WOUND INDUCED DEDIFFERENTIATION (WIND1) families. WUS and WIND positively control plant cell totipotency, while TCP negatively controls it. Interestingly, TCP is a transcriptional activator that acts as a negative regulator of shoot meristem formation, and WUS is a transcriptional repressor that positively maintains totipotency of the stem cells of the shoot meristem. We describe here the functions of TCP, WUS, and WIND transcription factors in the regulation of differentiation-dedifferentiation by positive and negative transcriptional regulators.

  1. Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania.

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    Frédéric Bringaud

    2007-09-01

    Full Text Available Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis, Trypanosoma brucei (sleeping sickness, and Trypanosoma cruzi (Chagas disease. Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements--LmSIDER1 (785 copies and LmSIDER2 (1,073 copies--that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are approximately 70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3'-untranslated regions (3'UTRs of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3'UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function.

  2. Transcription factor families in Arabidopsis: major progress and outstanding issues for future research.

    Science.gov (United States)

    Qu, Li-Jia; Zhu, Yu-Xian

    2006-10-01

    Transcription factors (TFs) are a group of proteins that control cellular processes by regulating the expression of downstream target genes. Recent progress has been made in the cloning and characterization of Arabidopsis TFs on the genome scale, especially on the cloning of open reading frames (ORFs), sequence analysis and the expression profiling of different TF families. Huge difference in numbers of subfamily members were found for Arabidopsis MYB, C2H2 (Zn), C3H-type 1 (Zn), C3H-type 2 (Zn) TFs by independent research groups, mainly because of differences in bioinformatic search stringency. However, the Arabidopsis and rice genomes contain very different numbers of TFs in the WRKY, NAC, bZIP, MADS, ALFIN-like, GRAS and C2C2 (Zn)-dof families, indicating a possible divergence of biological functions from dicots to monocots. TFs have also been found to play key roles in the biosynthesis and signaling of plant hormones, in cell growth and differentiation, and in photomorphogenesis.

  3. Targeted disruption of the CP2 gene, a member of the NTF family of transcription factors.

    Science.gov (United States)

    Ramamurthy, L; Barbour, V; Tuckfield, A; Clouston, D R; Topham, D; Cunningham, J M; Jane, S M

    2001-03-16

    The NTF-like family of transcription factors have been implicated in developmental regulation in organisms as diverse as Drosophila and man. The two mammalian members of this family, CP2 (LBP-1c/LSF) and LBP-1a (NF2d9), are highly related proteins sharing an overall amino acid identity of 72%. CP2, the best characterized of these factors, is a ubiquitously expressed 66-kDa protein that binds the regulatory regions of many diverse genes. Consequently, a role for CP2 has been proposed in globin gene expression, T-cell responses to mitogenic stimulation, and several other cellular processes. To elucidate the in vivo role of CP2, we have generated mice nullizygous for the CP2 allele. These animals were born in a normal Mendelian distribution and displayed no defects in growth, behavior, fertility, or development. Specifically, no perturbation of hematopoietic differentiation, globin gene expression, or immunological responses to T- and B-cell mitogenic stimulation was observed. RNA and protein analysis confirmed that the nullizygous mice expressed no full-length or truncated version of CP2. Electrophoretic mobility shift assays with nuclear extracts from multiple tissues demonstrated loss of CP2 DNA binding activity in the -/- lines. However, a slower migrating complex that was ablated with antiserum to NF2d9, the murine homologue of LBP-1a, was observed with these extracts. Furthermore, we demonstrate that recombinant LBP-1a can bind to known CP2 consensus sites and form protein complexes with previously defined heteromeric partners of CP2. These results suggest that LBP-1a/NF2d9 may compensate for loss of CP2 expression in vivo and that further analysis of the role of the NTF family of proteins requires the targeting of the NF2d9 gene.

  4. Involvement of the leucine response transcription factor LeuO in regulation of the genes for sulfa drug efflux.

    Science.gov (United States)

    Shimada, Tomohiro; Yamamoto, Kaneyoshi; Ishihama, Akira

    2009-07-01

    LeuO, a LysR family transcription factor, exists in a wide variety of bacteria of the family Enterobacteriaceae and is involved in the regulation of as yet unidentified genes affecting the stress response and pathogenesis expression. Using genomic screening by systematic evolution of ligands by exponential enrichment (SELEX) in vitro, a total of 106 DNA sequences were isolated from 12 different regions of the Escherichia coli genome. All of the SELEX fragments formed complexes in vitro with purified LeuO. After Northern blot analysis of the putative target genes located downstream of the respective LeuO-binding sequence, a total of nine genes were found to be activated by LeuO, while three genes were repressed by LeuO. The LeuO target gene collection included several multidrug resistance genes. A phenotype microarray assay was conducted to identify the gene(s) responsible for drug resistance and the drug species that are under the control of the LeuO target gene(s). The results described herein indicate that the yjcRQP operon, one of the LeuO targets, is involved in sensitivity control against sulfa drugs. We propose to rename the yjcRQP genes the sdsRQP genes (sulfa drug sensitivity determinant).

  5. The highly conserved Escherichia coli transcription factor YhaJ regulates aromatic compound degradation

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    Noa Palevsky

    2016-09-01

    Full Text Available The aromatic compound 2,4-dinitrotoluene (DNT, a common impurity in 2,4,6-trinitrotoluene (TNT production, has been suggested as a tracer for the presence of TNT-based landmines due to its stability and high volatility. We have previously described an Escherichia coli bioreporter capable of detecting the presence of DNT vapors, harboring a fusion of the yqjF gene promoter, to a reporter element. However, the DNT metabolite, which is the direct inducer of yqjF, has not yet been identified, nor has the regulatory mechanism of the induction been clarified. We demonstrate here that the YhaJ protein, a member of the LysR type family, acts as a transcriptional regulator of yqjF activation, as well as of a panel of additional E. coli genes. This group of genes share a common sequence motif in their promoters, which is suggested here as a putative YhaJ-box. In addition, we have linked YhaJ to the regulation of quinol-like compound degradation in the cell, and identified yhaK as playing a role in the degradation of DNT.

  6. YAP, TAZ, and Yorkie: a conserved family of signal-responsive transcriptional coregulators in animal development and human disease.

    Science.gov (United States)

    Wang, Kainan; Degerny, Cindy; Xu, Minghong; Yang, Xiang-Jiao

    2009-02-01

    How extracellular cues are transduced to the nucleus is a fundamental issue in biology. The paralogous WW-domain proteins YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif; also known as WWTR1, for WW-domain containing transcription regulator 1) constitute a pair of transducers linking cytoplasmic signaling events to transcriptional regulation in the nucleus. A cascade composed of mammalian Ste20-like (MST) and large tumor suppressor (LATS) kinases directs multisite phosphorylation, promotes 14-3-3 binding, and hinders nuclear import of YAP and TAZ, thereby inhibiting their transcriptional coactivator and growth-promoting activities. A similar cascade regulates the trafficking and function of Yorkie, the fly orthologue of YAP. Mammalian YAP and TAZ are expressed in various tissues and serve as coregulators for transcriptional enhancer factors (TEFs; also referred to as TEADs, for TEA-domain proteins), runt-domain transcription factors (Runxs), peroxisome proliferator-activated receptor gamma (PPARgamma), T-box transcription factor 5 (Tbx5), and several others. YAP and TAZ play distinct roles during mouse development. Both, and their upstream regulators, are intimately linked to tumorigenesis and other pathogenic processes. Here, we review studies on this family of signal-responsive transcriptional coregulators and emphasize how relative sequence conservation predicates their function and regulation, to provide a conceptual framework for organizing available information and seeking new knowledge about these signal transducers.

  7. Mblk-1 Transcription Factor Family: Its Roles in Various Animals and Regulation by NOL4 Splice Variants in Mammals

    Science.gov (United States)

    Takayanagi-Kiya, Seika; Kiya, Taketoshi; Kunieda, Takekazu; Kubo, Takeo

    2017-01-01

    Transcription factors play critical roles in regulation of neural development and functions. A transcription factor Mblk-1 was previously reported from a screen for factors possibly important for the higher brain functions of the honeybee. This review first summarizes how Mblk-1 was identified, and then provides an overview of the studies of Mblk-1 and their homologs. Mblk-1 family proteins are found broadly in animals and are shown to affect transcription activities. Studies have revealed that the mammalian homologs can interact with several cofactors and together regulate transcription. Interestingly, a recent study using the mouse homologs, Mlr1 and Mlr2, showed that one of their cofactor proteins, NOL4, have several splice variants with different effects on the transactivation activities of Mlr proteins. These findings suggest that there is an additional layer of the regulation of Mblk-1 family proteins by cofactor splice variants and provide novel insights into our current understanding of the roles of the conserved transcription factor family. PMID:28125049

  8. Gene structure, transcripts and calciotropic effects of the PTH family of peptides in Xenopus and chicken

    Directory of Open Access Journals (Sweden)

    Power Deborah M

    2010-12-01

    Full Text Available Abstract Background Parathyroid hormone (PTH and PTH-related peptide (PTHrP belong to a family of endocrine factors that share a highly conserved N-terminal region (amino acids 1-34 and play key roles in calcium homeostasis, bone formation and skeletal development. Recently, PTH-like peptide (PTH-L was identified in teleost fish raising questions about the evolution of these proteins. Although PTH and PTHrP have been intensively studied in mammals their function in other vertebrates is poorly documented. Amphibians and birds occupy unique phylogenetic positions, the former at the transition of aquatic to terrestrial life and the latter at the transition to homeothermy. Moreover, both organisms have characteristics indicative of a complex system in calcium regulation. This study investigated PTH family evolution in vertebrates with special emphasis on Xenopus and chicken. Results The PTH-L gene is present throughout the vertebrates with the exception of placental mammals. Gene structure of PTH and PTH-L seems to be conserved in vertebrates while PTHrP gene structure is divergent and has acquired new exons and alternative promoters. Splice variants of PTHrP and PTH-L are common in Xenopus and chicken and transcripts of the former have a widespread tissue distribution, although PTH-L is more restricted. PTH is widely expressed in fish tissue but from Xenopus to mammals becomes largely restricted to the parathyroid gland. The N-terminal (1-34 region of PTH, PTHrP and PTH-L in Xenopus and chicken share high sequence conservation and the capacity to modify calcium fluxes across epithelia suggesting a conserved role in calcium metabolism possibly via similar receptors. Conclusions The parathyroid hormone family contains 3 principal members, PTH, PTHrP and the recently identified PTH-L. In teleosts there are 5 genes which encode PTHrP (2, PTH (2 and PTH-L and in tetrapods there are 3 genes (PTHrP, PTH and PTH-L, the exception is placental mammals which

  9. The evolution of gene expression and binding specificity of the largest transcription factor family in primates.

    Science.gov (United States)

    Kapopoulou, Adamandia; Mathew, Lisha; Wong, Alex; Trono, Didier; Jensen, Jeffrey D

    2016-01-01

    The KRAB-containing zinc finger (KRAB-ZF) proteins represent the largest family of transcription factors (TFs) in humans, yet for the great majority, their function and specific genomic target remain unknown. However, it has been shown that a large fraction of these genes arose from segmental duplications, and that they have expanded in gene and zinc finger number throughout vertebrate evolution. To determine whether this expansion is linked to selective pressures acting on different domains, we have manually curated all KRAB-ZF genes present in the human genome together with their orthologous genes in three closely related species and assessed the evolutionary forces acting at the sequence level as well as on their expression profiles. We provide evidence that KRAB-ZFs can be separated into two categories according to the polymorphism present in their DNA-contacting residues. Those carrying a nonsynonymous single nucleotide polymorphism (SNP) in their DNA-contacting amino acids exhibit significantly reduced expression in all tissues, have emerged in a recent lineage, and seem to be less strongly constrained evolutionarily than those without such a polymorphism. This work provides evidence for a link between age of the TF, as well as polymorphism in their DNA-contacting residues and expression levels-both of which may be jointly affected by selection.

  10. Characterization of the MADS domain transcription factor family in Arabidopsis thaliana

    NARCIS (Netherlands)

    Folter, Stefan de

    2006-01-01

    Gene regulation at the level of transcription is crucial for almost all biological processes in a cell or organism. Transcription factors are sequence-specific DNA-binding proteins that are capable of activating and/or repressing transcription. The genome of Arabidopsis thaliana, for instance, consi

  11. AcEST: DK961394 [AcEST

    Lifescience Database Archive (English)

    Full Text Available : TrEMBL tr_hit_id Q11M45 Definition tr|Q11M45|Q11M45_MESSB Transcriptional regulator, LysR family OS=Mesorh......done Score E Sequences producing significant alignments: (bits) Value tr|Q11M45|Q11M45_MESSB Transcriptio...nal regulator, LysR family OS... 33 8.3 >tr|Q11M45|Q11M45_MESSB Transcriptional regulator, LysR family OS=Me

  12. Multiple DNA-binding modes for the ETS family transcription factor PU.1.

    Science.gov (United States)

    Esaki, Shingo; Evich, Marina G; Erlitzki, Noa; Germann, Markus W; Poon, Gregory M K

    2017-09-29

    The eponymous DNA-binding domain of ETS (E26 transformation-specific) transcription factors binds a single sequence-specific site as a monomer over a single helical turn. Following our previous observation by titration calorimetry that the ETS member PU.1 dimerizes sequentially at a single sequence-specific DNA-binding site to form a 2:1 complex, we have carried out an extensive spectroscopic and biochemical characterization of site-specific PU.1 ETS complexes. Whereas 10 bp of DNA was sufficient to support PU.1 binding as a monomer, additional flanking bases were required to invoke sequential dimerization of the bound protein. NMR spectroscopy revealed a marked loss of signal intensity in the 2:1 complex, and mutational analysis implicated the distal surface away from the bound DNA as the dimerization interface. Hydroxyl radical DNA footprinting indicated that the site-specifically bound PU.1 dimers occupied an extended DNA interface downstream from the 5'-GGAA-3' core consensus relative to its 1:1 counterpart, thus explaining the apparent site size requirement for sequential dimerization. The site-specifically bound PU.1 dimer resisted competition from nonspecific DNA and showed affinities similar to other functionally significant PU.1 interactions. As sequential dimerization did not occur with the ETS domain of Ets-1, a close structural homolog of PU.1, 2:1 complex formation may represent an alternative autoinhibitory mechanism in the ETS family at the protein-DNA level. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Krüppel-like family of transcription factors: an emerging new frontier in fat biology

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    Christopher W. Brey, Mark P. Nelder, Tiruneh Hailemariam, Randy Gaugler, Sarwar Hashmi

    2009-01-01

    Full Text Available In mammals, adipose tissue stores energy in the form of fat. The ability to regulate fat storage is essential for the growth, development and reproduction of most animals, thus any abnormalities caused by excess fat accumulation can result in pathological conditions which are linked to several interrelated diseases, such as cardiovascular diseases, diabetes, and obesity. In recent years significant effort has been applied to understand basic mechanism of fat accumulation in mammalian system. Work in mouse has shown that the family of Krüppel-like factors (KLFs, a conserved and important class of transcription factors, regulates adipocyte differentiation in mammals. However, how fat storage is coordinated in response to positive and negative feedback signals is still poorly understood. To address mechanisms underlying fat storage we have studied two Caenorhabditis elegans KLFs and demonstrate that both worm klfs are key regulators of fat metabolism in C. elegans. These results provide the first in vivo evidence supporting essential regulatory roles for KLFs in fat metabolism in C. elegans and shed light on the human counterpart in disease-gene association. This finding allows us to pursue a more comprehensive approach to understand fat biology and provides an opportunity to learn about the cascade of events that regulate KLF activation, repression and interaction with other factors in exerting its biological function at an organismal level. In this review, we provide an overview of the most current information on the key regulatory components in fat biology, synthesize the diverse literature, pose new questions, and propose a new model organism for understanding fat biology using KLFs as the central theme.

  14. Homology modeling and validation of SAS2271 transcriptional regulator of AraC family in Staphylococcus aureus

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    Money Gupta

    2013-02-01

    Full Text Available Objective: To predict three dimensional structure of AraC Family transcription regulator protein in staphylococcus aureus involved in causing virulence. Methods: Evolutionary dynamics of S. aureus reveled that several mutations preceding virulence lead to truncated proteins that plays an important role in virulence. The Structural templates are identified using homology search and then homology modelling is used to get the 3-D structure of the protein. Results: The 3-D structure of SAS2271 transcriptional factor of AraC family in MSSA476 strain of S. aureus was modelled and validated using the Ramachandran plot. Conclusions: The knowledge of 3-D structure of the protein will be helpful in identifying its biochemical function along with its regulatory mechanism in causing virulence.

  15. The Serratia LuxR family regulator CarR 39006 activates transcription independently of cognate quorum sensing signals.

    Science.gov (United States)

    Poulter, Simon; Carlton, Timothy M; Spring, David R; Salmond, George P C

    2011-05-01

    In Gram-negative bacteria, quorum sensing control of gene expression is mediated by transcription factors of the LuxR family, whose DNA-binding affinity is modulated by diffusible N-acyl homoserine lactone (AHL) signalling molecules. In Serratia sp. ATCC 39006 and the plant pathogen Erwinia carotovora ssp. carotovora (Ecc), the biosynthesis of the β-lactam antibiotic 1-carbapen-2-em-3-carboxylic acid (Car) is under quorum sensing control. This study has revealed that, uniquely, the LuxR family transcriptional activator CarR(39006) from Serratia 39006 has no detectable affinity for cognate AHL molecules. Furthermore, CarR(39006) was shown to be naturally competent to bind to its target promoter with high affinity, activate transcription and resist cellular proteolysis, and was unaffected by AHL signals. Experiments with chimeric proteins suggest that the C-terminal DNA-binding domain of CarR(39006) may be responsible for conferring AHL independence. In contrast, we show that the homologous CarR(Ecc) protein binds to its 3O-C6-HSL ligand with high affinity, and that the highly conserved Trp-44 residue is critical for this interaction. Unlike TraR from Agrobacterium tumefaciens, CarR(Ecc) is not directly protected from cellular proteolysis by AHL binding, but via AHL-induced DNA binding. At physiological protein concentrations, AHL binding induces CarR(Ecc) to bind to its target promoter with higher affinity and activate transcription. © 2011 Blackwell Publishing Ltd.

  16. Computer-Based Annotation of Putative AraC/XylS-Family Transcription Factors of Known Structure but Unknown Function

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    Andreas Schüller

    2012-01-01

    Full Text Available Currently, about 20 crystal structures per day are released and deposited in the Protein Data Bank. A significant fraction of these structures is produced by research groups associated with the structural genomics consortium. The biological function of many of these proteins is generally unknown or not validated by experiment. Therefore, a growing need for functional prediction of protein structures has emerged. Here we present an integrated bioinformatics method that combines sequence-based relationships and three-dimensional (3D structural similarity of transcriptional regulators with computer prediction of their cognate DNA binding sequences. We applied this method to the AraC/XylS family of transcription factors, which is a large family of transcriptional regulators found in many bacteria controlling the expression of genes involved in diverse biological functions. Three putative new members of this family with known 3D structure but unknown function were identified for which a probable functional classification is provided. Our bioinformatics analyses suggest that they could be involved in plant cell wall degradation (Lin2118 protein from Listeria innocua, PDB code 3oou, symbiotic nitrogen fixation (protein from Chromobacterium violaceum, PDB code 3oio, and either metabolism of plant-derived biomass or nitrogen fixation (protein from Rhodopseudomonas palustris, PDB code 3mn2.

  17. TCPs, WUSs, and WINDs: Families of transcription factors that regulate shoot meristem formation, stem cell maintenance, and somatic cell differentiation

    Directory of Open Access Journals (Sweden)

    Miho eIkeda

    2014-09-01

    Full Text Available In contrast to somatic mammalian cells, which cannot alter their fate, plant cells can dedifferentiate to form totipotent callus cells and regenerate a whole plant, following treatment with specific phytohormones. However, the regulatory mechanisms and key factors that control differentiation-dedifferentiation and cell totipotency have not been completely clarified in plants. Recently, several plant transcription factors that regulate meristem formation and dedifferentiation have been identified and include members of the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP, WUSCHEL (WUS, and WOUND INDUCED DEDIFFERENTIATION (WIND1 families. WUS and WIND positively control plant cell totipotency, while TCP negatively controls it. Interestingly, TCP is a transcriptional activator that acts as a negative regulator of shoot meristem formation, and WUS is a transcriptional repressor that positively maintains totipotency of the stem cells of the shoot meristem. We describe here the functions of TCP, WUS and WIND transcription factors in the regulation of differentiation-dedifferentiation by positive and negative transcriptional regulators.

  18. Members of the TEAD family of transcription factors regulate the expression of Myf5 in ventral somitic compartments.

    Science.gov (United States)

    Ribas, Ricardo; Moncaut, Natalia; Siligan, Christine; Taylor, Kevin; Cross, Joe W; Rigby, Peter W J; Carvajal, Jaime J

    2011-07-15

    The transcriptional regulation of the Mrf4/Myf5 locus depends on a multitude of enhancers that, in equilibria with transcription balancing sequences and the promoters, regulate the expression of the two genes throughout embryonic development and in the adult. Transcription in a particular set of muscle progenitors can be driven by the combined outputs of several enhancers that are not able to recapitulate the entire expression pattern in isolation, or by the action of a single enhancer the activity of which in isolation is equivalent to that within the context of the locus. We identified a new enhancer element of this second class, ECR111, which is highly conserved in all vertebrate species and is necessary and sufficient to drive Myf5 expression in ventro-caudal and ventro-rostral somitic compartments in the mouse embryo. EMSA analyses and data obtained from binding-site mutations in transgenic embryos show that a binding site for a TEA Domain (TEAD) transcription factor is essential for the function of this new enhancer, while ChIP assays show that at least two members of the family of transcription factors bind to it in vivo. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Transcriptional profiling in C. elegans suggests DNA damage dependent apoptosis as an ancient function of the p53 family

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    Rothblatt Jonathan

    2008-07-01

    Full Text Available Abstract Background In contrast to the three mammalian p53 family members, p53, which is generally involved in DNA damage responses, and p63 and p73 which are primarily needed for developmental regulation, cep-1 encodes for the single C. elegans p53-like gene. cep-1 acts as a transcription activator in a primordial p53 pathway that involves CEP-1 activation and the CEP-1 dependent transcriptional induction of the worm BH3 only domain encoding genes egl-1 and ced-13 to induce germ cell apoptosis. EGL-1 and CED-13 proteins inactivate Bcl-2 like CED-9 to trigger CED-4 and CED-3 caspase dependent germ cell apoptosis. To address the function of p53 in global transcriptional regulation we investigate genome-wide transcriptional responses upon DNA damage and cep-1 deficiency. Results Examining C. elegans expression profiles using whole genome Affymetrix GeneChip arrays, we found that 83 genes were induced more than two fold upon ionizing radiation (IR. None of these genes, with exception of an ATP ribosylase homolog, encode for known DNA repair genes. Using two independent cep-1 loss of function alleles we did not find genes regulated by cep-1 in the absence of IR. Among the IR-induced genes only three are dependent on cep-1, namely egl-1, ced-13 and a novel C. elegans specific gene. The majority of IR-induced genes appear to be involved in general stress responses, and qRT-PCR experiments indicate that they are mainly expressed in somatic tissues. Interestingly, we reveal an extensive overlap of gene expression changes occurring in response to DNA damage and in response to bacterial infection. Furthermore, many genes induced by IR are also transcriptionally regulated in longevity mutants suggesting that DNA damage and aging induce an overlapping stress response. Conclusion We performed genome-wide gene expression analyses which indicate that only a surprisingly small number of genes are regulated by CEP-1 and that DNA damage induced apoptosis via the

  20. Regulation of gene expression at the beginning of mammalian development and the TEAD family of transcription factors.

    Science.gov (United States)

    Kaneko, K J; DePamphilis, M L

    1998-01-01

    In mouse development, transcription is first detected in late 1-cell embryos, but translation of newly synthesized transcripts does not begin until the 2-cell stage. Thus, the onset of zygotic gene expression (ZGE) is regulated at the level of both transcription and translation. Chromatin-mediated repression is established after formation of a 2-cell embryo, concurrent with the developmental acquisition of enhancer function. The most effective enhancer in cleavage stage mouse embryos depends on DNA binding sites for TEF-1, the prototype for a family of transcription factors that share the same TEA DNA binding domain. Mice contain at least four, and perhaps five, genes with the same TEA DNA binding domain (mTEAD genes). Since mTEAD-2 is the only one expressed during the first 7 days of mouse development, it is most likely responsible for the TEAD transcription factor activity that first appears at the beginning of ZGE. All four mTEAD genes are expressed at later embryonic stages and in adult tissues; virtually every tissue expresses at least one family member, consistent with a critical role for TEAD proteins in either cell proliferation or differentiation. The 72-amino acid TEA DNA binding domains in mTEAD-2, 3, and 4 are approximately 99% homologous to the same domain in mTEAD-1, and all four proteins bind specifically to the same DNA sequences in vitro with a Kd value of 16-38 nM DNA. Since TEAD proteins appear to be involved in both activation and repression of different genes and do not appear to be functionally redundant, differential activity of TEAD proteins must result either from association with other proteins or from differential sensitivity to chromatin-packaged DNA binding sites.

  1. Comparative Analysis of Transcription Factors Families across Fungal Tree of Life

    Energy Technology Data Exchange (ETDEWEB)

    Salamov, Asaf; Grigoriev, Igor

    2015-03-19

    Transcription factors (TFs) are proteins that regulate the transcription of genes, by binding to specific DNA sequences. Based on literature (Shelest, 2008; Weirauch and Hughes,2011) collected and manually curated list of DBD Pfam domains (in total 62 DBD domains) We looked for distribution of TFs in 395 fungal genomes plus additionally in plant genomes (Phytozome), prokaryotes(IMG), some animals/metazoans and protists genomes

  2. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria.

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Iñigo; Novick, Richard P; Christie, Gail E; Penadés, José R

    2013-08-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria.

  3. A super-family of transcriptional activators regulates bacteriophage packaging and lysis in Gram-positive bacteria

    Science.gov (United States)

    Quiles-Puchalt, Nuria; Tormo-Más, María Ángeles; Campoy, Susana; Toledo-Arana, Alejandro; Monedero, Vicente; Lasa, Íñigo; Novick, Richard P.; Christie, Gail E.; Penadés, José R.

    2013-01-01

    The propagation of bacteriophages and other mobile genetic elements requires exploitation of the phage mechanisms involved in virion assembly and DNA packaging. Here, we identified and characterized four different families of phage-encoded proteins that function as activators required for transcription of the late operons (morphogenetic and lysis genes) in a large group of phages infecting Gram-positive bacteria. These regulators constitute a super-family of proteins, here named late transcriptional regulators (Ltr), which share common structural, biochemical and functional characteristics and are unique to this group of phages. They are all small basic proteins, encoded by genes present at the end of the early gene cluster in their respective phage genomes and expressed under cI repressor control. To control expression of the late operon, the Ltr proteins bind to a DNA repeat region situated upstream of the terS gene, activating its transcription. This involves the C-terminal part of the Ltr proteins, which control specificity for the DNA repeat region. Finally, we show that the Ltr proteins are the only phage-encoded proteins required for the activation of the packaging and lysis modules. In summary, we provide evidence that phage packaging and lysis is a conserved mechanism in Siphoviridae infecting a wide variety of Gram-positive bacteria. PMID:23771138

  4. The role of ATF-2 family transcription factors in adipocyte differentiation: antiobesity effects of p38 inhibitors.

    Science.gov (United States)

    Maekawa, Toshio; Jin, Wanzhu; Ishii, Shunsuke

    2010-02-01

    ATF-2 is a member of the ATF/CREB family of transcription factors and is activated by stress-activated protein kinases, such as p38. To analyze the physiological role of ATF-2 family transcription factors, we have generated mice with mutations in Atf-2 and Cre-bpa, an Atf-2-related gene. The trans-heterozygotes of both mutants were lean and had reduced white adipose tissue (WAT). ATF-2 and CRE-BPa were required for bone morphogenetic protein 2 (BMP-2)-and p38-dependent induction of peroxisome proliferator-activated receptor gamma2 (PPARgamma2), a key transcription factor mediating adipocyte differentiation. Since stored fat supplies have been recognized as a possible target for antiobesity treatments, we tested whether inhibition of the p38-ATF-2 pathway suppresses adipocyte differentiation and leads to reduced WAT by treating mice with a p38 inhibitor for long periods of time. High-fat diet (HFD)-induced obesity was significantly reduced in mice fed the p38 inhibitor. Furthermore, the p38 inhibitor alleviated HFD-induced insulin resistance. In p38 inhibitor-treated mice, macrophage infiltration into WAT was reduced and the tumor necrosis factor alpha (TNF-alpha) levels were lower than control mice. Thus, p38 inhibitors may provide a novel antiobesity treatment.

  5. The plant-specific Dof transcription factors family: new players involved in vascular system development and functioning in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Rozenn eLe Hir

    2013-05-01

    Full Text Available In higher plants phloem and xylem are responsible for long-distance transport of water, nutrients, and signals that act systemically at short or long distance to coordinate developmental processes. The formation of the plant vascular system is a complex process that integrates signalling events and gene regulation at transcriptional and posttranscriptional levels. Thanks to transcriptomic and proteomic analysis we start to better understand the mechanisms underlying the formation and the functioning of the vascular system. The role of the DNA-binding with one finger (Dof TFs, a group of plant–specific transcription factors, recently emerged as part of the transcriptional regulatory networks acting on the formation and functioning of the vascular tissues. More than half of the members of this TF family are expressed in the vascular system. In addition some of them have been proposed to be mobile proteins, suggesting a possible role in the control of short- or long-distance signalling as well. This review summarizes the current knowledge on Dof TFs family in Arabidopsis with a special focus on their role in vascular development and functioning.

  6. Genome-wide analysis and expression profiling of the ERF transcription factor family in potato (Solanum tuberosum L.).

    Science.gov (United States)

    Charfeddine, Mariam; Saïdi, Mohamed Najib; Charfeddine, Safa; Hammami, Asma; Gargouri Bouzid, Radhia

    2015-04-01

    The ERF transcription factors belong to the AP2/ERF superfamily, one of the largest transcription factor families in plants. They play important roles in plant development processes, as well as in the response to biotic, abiotic, and hormone signaling. In the present study, 155 putative ERF transcription factor genes were identified from the potato (Solanum tuberosum) genome database, and compared with those from Arabidopsis thaliana. The StERF proteins are divided into ten phylogenetic groups. Expression analyses of five StERFs were carried out by semi-quantitative RT-PCR and compared with published RNA-seq data. These latter analyses were used to distinguish tissue-specific, biotic, and abiotic stress genes as well as hormone-responsive StERF genes. The results are of interest to better understand the role of the AP2/ERF genes in response to diverse types of stress in potatoes. A comprehensive analysis of the physiological functions and biological roles of the ERF family genes in S. tuberosum is required to understand crop stress tolerance mechanisms.

  7. Gclust Server: 29557 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available al regulator of oxidative stress, regulates intracellular hydrogen peroxide (LysR family) 3 1.00e-16 0.0 0.0... Representative annotation transcriptional regulator of oxidative stress, regulates intracellular hydrogen p

  8. The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway.

    Science.gov (United States)

    Wu, Shian; Liu, Yi; Zheng, Yonggang; Dong, Jixin; Pan, Duojia

    2008-03-01

    The Hippo (Hpo) kinase cascade restricts tissue growth by inactivating the transcriptional coactivator Yorkie (Yki), which regulates the expression of target genes such as the cell death inhibitor diap1 by unknown mechanisms. Here we identify the TEAD/TEF family protein Scalloped (Sd) as a DNA-binding transcription factor that partners with Yki to mediate the transcriptional output of the Hpo growth-regulatory pathway. The diap1 (th) locus harbors a minimal Sd-binding Hpo Responsive Element (HRE) that mediates transcriptional regulation by the Hpo pathway. Sd binds directly to Yki, and a Yki missense mutation that abrogates Sd-Yki binding also inactivates Yki function in vivo. We further demonstrate that sd is required for yki-induced tissue overgrowth and target gene expression, and that sd activity is conserved in its mammalian homolog. Our results uncover a heretofore missing link in the Hpo signaling pathway and provide a glimpse of the molecular events on a Hpo-responsive enhancer element.

  9. Regulation of expression of two LY-6 family genes by intron retention and transcription induced chimerism

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    Mallya Meera

    2008-09-01

    Full Text Available Abstract Background Regulation of the expression of particular genes can rely on mechanisms that are different from classical transcriptional and translational control. The LY6G5B and LY6G6D genes encode LY-6 domain proteins, whose expression seems to be regulated in an original fashion, consisting of an intron retention event which generates, through an early premature stop codon, a non-coding transcript, preventing expression in most cell lines and tissues. Results The MHC LY-6 non-coding transcripts have shown to be stable and very abundant in the cell, and not subject to Nonsense Mediated Decay (NMD. This retention event appears not to be solely dependent on intron features, because in the case of LY6G5B, when the intron is inserted in the artificial context of a luciferase expression plasmid, it is fully spliced but strongly stabilises the resulting luciferase transcript. In addition, by quantitative PCR we found that the retained and spliced forms are differentially expressed in tissues indicating an active regulation of the non-coding transcript. EST database analysis revealed that these genes have an alternative expression pathway with the formation of Transcription Induced Chimeras (TIC. This data was confirmed by RT-PCR, revealing the presence of different transcripts that would encode the chimeric proteins CSNKβ-LY6G5B and G6F-LY6G6D, in which the LY-6 domain would join to a kinase domain and an Ig-like domain, respectively. Conclusion In conclusion, the LY6G5B and LY6G6D intron-retained transcripts are not subjected to NMD and are more abundant than the properly spliced forms. In addition, these genes form chimeric transcripts with their neighbouring same orientation 5' genes. Of interest is the fact that the 5' genes (CSNKβ or G6F undergo differential splicing only in the context of the chimera (CSNKβ-LY6G5B or G6F-LY6G6C and not on their own.

  10. Paradoxical role of an Egr transcription factor family member, Egr2/Krox20, in learning and memory

    Directory of Open Access Journals (Sweden)

    Roseline Poirier

    2007-12-01

    Full Text Available It is well established that Egr1/zif268, a member of the Egr family of transcription factors, is critical for the consolidation of several forms of memories. Recently, the Egr3 family member has also been implicated in learning and memory. Because Egr family members encode closely related zinc-finger transcription factors sharing a highly homologous DNA binding domain that recognises the same DNA sequence, they may have related functions in brain. Another Egr family member expressed in brain, Egr2/Krox20 is known to be crucial for normal hindbrain development and has been implicated in several inherited peripheral neuropathies; however, due to Egr2-null mice perinatal lethality, its potential role in cognitive functions in the adult has not been yet explored. Here, we generated Egr2 conditional mutant mice allowing postnatal, forebrain-specific Cre-mediated Egr2 excision and tested homozygous, heterozygous and control littermates on a battery of behavioural tasks to evaluate motor capacity, exploratory behaviour, emotional reactivity and learning and memory performance in spatial and non-spatial tasks. Egr2-deficient mice had no sign of locomotor, exploratory or anxiety disturbances. Surprisingly, they also had no impairment in spatial learning and memory, taste aversion memory or fear memory using a trace conditioning paradigm. On the contrary, Egr2-deficient mice had improved performance in motor learning on a rotarod, and in object recognition memory. These results clearly do not extend the phenotypic consequences resulting from either Egr1 or Egr3 loss-of-function to Egr2. In contrast, they indicate that Egr family members may have different, and in certain circumstances antagonistic functions in the adult brain.

  11. Genome-wide systematic characterization of the bZIP transcriptional factor family in tomato (Solanum lycopersicum L.).

    Science.gov (United States)

    Li, Dayong; Fu, Fuyou; Zhang, Huijuan; Song, Fengming

    2015-10-12

    Transcription factors of the basic leucine zipper (bZIP) family represent exclusively in eukaryotes and have been shown to regulate diverse biological processes in plant growth and development as well as in abiotic and biotic stress responses. However, little is known about the bZIP family in tomato (Solanum lycopersicum L.). The SlbZIP genes were identified using local BLAST and hidden Markov model profile searches. The phylogenetic trees, conserved motifs and gene structures were generated by MEGA6.06, MEME tool and gene Structure Display Server, respectively. The syntenic block diagrams were generated by the Circos software. The transcriptional gene expression profiles were obtained using Genevestigator tool and quantitative RT-PCR. In the present study, we carried out a genome-wide identification and systematic analyses of 69 SlbZIP genes that distributes unevenly on the tomato chromosomes. This family can be divided into 9 groups according to the phylogenetic relationship among the SlbZIP proteins. Six kinds of intron patterns (a-f) within the basic and hinge regions are defined. The additional conserved motifs and their presence of the group specificity were also identified. Further, we predicted the DNA-binding patterns and the dimerization property on the basis of the characteristic features in the basic and hinge regions and the leucine zipper, respectively, which supports our classification greatly and helps to classify 24 distinct subfamilies. Within the SlbZIP family, a total of 40 SlbZIP genes are located in the segmental duplicate regions in the tomato genome, suggesting that the segment chromosomal duplications contribute greatly to the expansion of the tomato SlbZIP family. Expression profiling analyses of 59 SlbZIP genes using quantitative RT-PCR and publicly available microarray data indicate that the tomato SlbZIP genes have distinct and diverse expression patterns in different tissues and developmental stages and many of the tomato bZIP genes

  12. Reverse Transcription-PCR Analysis of the Regulation of the Manganese Peroxidase Gene Family

    OpenAIRE

    Gettemy, Jessica M.; Ma, Biao; Alic, Margaret; Gold, Michael H.

    1998-01-01

    Manganese peroxidase (MnP) gene expression in the lignin-degrading fungus Phanerochaete chrysosporium is regulated by nutrient nitrogen levels and by Mn(II), the substrate for the enzyme, as well as by heat shock and other factors. Reverse transcription-PCR (RT-PCR) of total RNA can distinguish the mRNAs of each of the three sequenced P. chrysosporium mnp genes, i.e., mnp1, mnp2, and mnp3. Quantitative RT-PCR demonstrates that each of the three transcripts is present at a similar low basal le...

  13. Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Thomas L Rodgers

    2013-09-01

    Full Text Available Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change. The mechanisms, however, for communicating dynamic fluctuations between sites are debated. We provide a foundational theory for how allostery can occur as a function of low-frequency dynamics without a change in structure. We have generated coarse-grained models that describe the protein backbone motions of the CRP/FNR family transcription factors, CAP of Escherichia coli and GlxR of Corynebacterium glutamicum. The latter we demonstrate as a new exemplar for allostery without conformation change. We observe that binding the first molecule of cAMP ligand is correlated with modulation of the global normal modes and negative cooperativity for binding the second cAMP ligand without a change in mean structure. The theory makes key experimental predictions that are tested through an analysis of variant proteins by structural biology and isothermal calorimetry. Quantifying allostery as a free energy landscape revealed a protein "design space" that identified the inter- and intramolecular regulatory parameters that frame CRP/FNR family allostery. Furthermore, through analyzing CAP variants from diverse species, we demonstrate an evolutionary selection pressure to conserve residues crucial for allosteric control. This finding provides a link between the position of CRP/FNR transcription factors within the allosteric free energy landscapes and evolutionary selection pressures. Our study therefore reveals significant features of the mechanistic basis for allostery. Changes in low-frequency dynamics correlate with allosteric effects on ligand binding without the requirement for a defined spatial pathway. In addition to evolving suitable three-dimensional structures, CRP/FNR family transcription factors have

  14. Inheritance and memory of stress-induced epigenome change: roles played by the ATF-2 family of transcription factors

    Science.gov (United States)

    Seong, Ki-Hyeon; Maekawa, Toshio; Ishii, Shunsuke

    2012-01-01

    Data on the inheritance-of-stress effect have been accumulating and some mechanistic insights, such as epigenetic regulation, have also been suggested. In particular, the modern view of Lamarckian inheritance appears to be affected by the finding that stress-induced epigenetic changes can be inherited. This review summarizes the current data on the inheritance of stress effect and possible mechanisms involved in this process. In particular, we focus on the stress-induced epigenetic changes mediated by the ATF-2 family of transcription factors. PMID:22380515

  15. Genome-wide analysis of the Dof transcription factor gene family reveals soybean-specific duplicable and functional characteristics.

    Directory of Open Access Journals (Sweden)

    Yong Guo

    Full Text Available The Dof domain protein family is a classic plant-specific zinc-finger transcription factor family involved in a variety of biological processes. There is great diversity in the number of Dof genes in different plants. However, there are only very limited reports on the characterization of Dof transcription factors in soybean (Glycine max. In the present study, 78 putative Dof genes were identified from the whole-genome sequence of soybean. The predicted GmDof genes were non-randomly distributed within and across 19 out of 20 chromosomes and 97.4% (38 pairs were preferentially retained duplicate paralogous genes located in duplicated regions of the genome. Soybean-specific segmental duplications contributed significantly to the expansion of the soybean Dof gene family. These Dof proteins were phylogenetically clustered into nine distinct subgroups among which the gene structure and motif compositions were considerably conserved. Comparative phylogenetic analysis of these Dof proteins revealed four major groups, similar to those reported for Arabidopsis and rice. Most of the GmDofs showed specific expression patterns based on RNA-seq data analyses. The expression patterns of some duplicate genes were partially redundant while others showed functional diversity, suggesting the occurrence of sub-functionalization during subsequent evolution. Comprehensive expression profile analysis also provided insights into the soybean-specific functional divergence among members of the Dof gene family. Cis-regulatory element analysis of these GmDof genes suggested diverse functions associated with different processes. Taken together, our results provide useful information for the functional characterization of soybean Dof genes by combining phylogenetic analysis with global gene-expression profiling.

  16. Genome-wide analysis of basic leucine zipper transcription factor families in Arabidopsis thaliana, Oryza saliva and Populus trichocarpa

    Institute of Scientific and Technical Information of China (English)

    JI Qian; ZHANG Liang-sheng; WANG Yi-fei; WANG Jian

    2009-01-01

    The basic leucine zipper (bZIP) transcription factors form a large gene family that is important in pathogen defense, light and stress signaling, etc. The Completed whole genome sequences of model plants Arabidopsis (Arabidopsis thaliana), rice (Oryza saliva) and poplar (Populus trichocarpa) constitute a valuable resource for genome-wide analysis and genomic comparative analysis, as they are representatives of the two major evolutionary lineages within the angiosperms: the monocotyledons and the dicotyledons. In this study, bioinformatics analysis identified 74, 89 and 88 bZIP genes respectively in Arabidopsis, rice and poplar. Moreover, a comprehensive overview of this gene family is presented, including the gene structure, phylogeny, chromosome distribution, conserved motifs. As a result, the plant bZIPs were organized into 10 subfamilies on basis of phylogenetic relationship. Gene duplication events during the family evolution history were also investigated. And it was further concluded that chromosomal/segmental duplication might have played a key role in gene expansion of bZIP gene family.

  17. Genome-wide analysis of the R2R3-MYB transcription factor gene family in sweet orange (Citrus sinensis).

    Science.gov (United States)

    Liu, Chaoyang; Wang, Xia; Xu, Yuantao; Deng, Xiuxin; Xu, Qiang

    2014-10-01

    MYB transcription factor represents one of the largest gene families in plant genomes. Sweet orange (Citrus sinensis) is one of the most important fruit crops worldwide, and recently the genome has been sequenced. This provides an opportunity to investigate the organization and evolutionary characteristics of sweet orange MYB genes from whole genome view. In the present study, we identified 100 R2R3-MYB genes in the sweet orange genome. A comprehensive analysis of this gene family was performed, including the phylogeny, gene structure, chromosomal localization and expression pattern analyses. The 100 genes were divided into 29 subfamilies based on the sequence similarity and phylogeny, and the classification was also well supported by the highly conserved exon/intron structures and motif composition. The phylogenomic comparison of MYB gene family among sweet orange and related plant species, Arabidopsis, cacao and papaya suggested the existence of functional divergence during evolution. Expression profiling indicated that sweet orange R2R3-MYB genes exhibited distinct temporal and spatial expression patterns. Our analysis suggested that the sweet orange MYB genes may play important roles in different plant biological processes, some of which may be potentially involved in citrus fruit quality. These results will be useful for future functional analysis of the MYB gene family in sweet orange.

  18. Molecular evolution and gene expression differences within the HD-Zip transcription factor family of Zea mays L.

    Science.gov (United States)

    Mao, Hude; Yu, Lijuan; Li, Zhanjie; Liu, Hui; Han, Ran

    2016-04-01

    Homeodomain-leucine zipper (HD-Zip) transcription factors regulate developmental processes and stress responses in plants, and they vary widely in gene number and family structure. In this study, 55 predicted maize HD-Zip genes were systematically analyzed with respect to their phylogenetic relationships, molecular evolution, and gene expression in order to understand the functional diversification within the family. Phylogenetic analysis of HD-Zip proteins from Zea mays, Oryza sativa, Arabidopsis thaliana, Vitis vinifera, and Physcomitrella patens showed that they group into four classes. We inferred that the copy numbers of classes I and III genes were relatively conserved in all five species. The 55 maize HD-Zip genes are distributed randomly on the ten chromosomes, with 15 segmental duplication and 4 tandem duplication events, suggesting that segmental duplications were the major contributors in the expansion of the maize HD-Zip gene family. Expression analysis of the 55 maize HD-Zip genes in different tissues and drought conditions revealed differences in the expression levels and patterns between the four classes. Promoter analysis revealed that a number of stress response-, hormone response-, light response-, and development-related cis-acting elements were present in their promoters. Our results provide novel insights into the molecular evolution and gene expression within the HD-Zip gene family in maize, and provide a solid foundation for future functional study of the HD-Zip genes in maize.

  19. Reverse Genetic Analysis of Transcription FactorOsHox9, a Member of Homeobox Family, in Rice

    Institute of Scientific and Technical Information of China (English)

    AI Li-ping; SHEN Ao; GAO Zhi-chao; LI Zheng-long; SUN Qiong-lin; LI Ying-ying; LUAN Wei-jiang

    2014-01-01

    Homeobox transcription factors participate in the growth and development of plants by regulating cell differentiation, morphogenesis and environmental signal response. To reveal the functions of these transcription factors in rice, we constructed the RNAi vectors ofOsHox9, a member of homeobox family, and analyzed the function ofOsHox9 using reverse genetics. The plant height and tillering number of RNAi transgenic plants decreased compared with those of wild-type plants. Reverse transcription-polymerase chain reaction analysis showed thatOsHox9 expression reduced in the transgenic plants with phenotypic variance, whereas that in the transgenic plants without phenotypic variance was similar to that in the wild-type plants. This result suggests that the phenotypes of the transgenic plants were caused by RNAi effects. The tissue-specificity ofOsHox9 expression indicated that it was expressed in different organs, with high expression in stem apical meristem and young panicles. Subcelular location ofOsHox9 demonstrated that it was localized on the cell membrane.

  20. The ETS Family Transcription Factors Etv5 and PU.1 Function in Parallel To Promote Th9 Cell Development.

    Science.gov (United States)

    Koh, Byunghee; Hufford, Matthew M; Pham, Duy; Olson, Matthew R; Wu, Tong; Jabeen, Rukhsana; Sun, Xin; Kaplan, Mark H

    2016-09-15

    The IL-9-secreting Th9 subset of CD4 Th cells develop in response to an environment containing IL-4 and TGF-β, promoting allergic disease, autoimmunity, and resistance to pathogens. We previously identified a requirement for the ETS family transcription factor PU.1 in Th9 development. In this report, we demonstrate that the ETS transcription factor ETS variant 5 (ETV5) promotes IL-9 production in Th9 cells by binding and recruiting histone acetyltransferases to the Il9 locus at sites distinct from PU.1. In cells that are deficient in both PU.1 and ETV5 there is lower IL-9 production than in cells lacking either factor alone. In vivo loss of PU.1 and ETV5 in T cells results in distinct effects on allergic inflammation in the lung, suggesting that these factors function in parallel. Together, these data define a role for ETV5 in Th9 development and extend the paradigm of related transcription factors having complementary functions during differentiation.

  1. Global Expressions Landscape of NAC Transcription Factor Family and Their Responses to Abiotic Stresses in Citrullus lanatus.

    Science.gov (United States)

    Lv, Xiaolong; Lan, Shanrong; Guy, Kateta Malangisha; Yang, Jinghua; Zhang, Mingfang; Hu, Zhongyuan

    2016-08-05

    Watermelon (Citrullus lanatus) is one xerophyte that has relative higher tolerance to drought and salt stresses as well as more sensitivity to cold stress, compared with most model plants. These characteristics facilitate it a potential model crop for researches on salt, drought or cold tolerance. In this study, a genome-wide comprehensive analysis of the ClNAC transcription factor (TF) family was carried out for the first time, to investigate their transcriptional profiles and potential functions in response to these abiotic stresses. The expression profiling analysis reveals that several NAC TFs are highly responsive to abiotic stresses and development, for instance, subfamily IV NACs may play roles in maintaining water status under drought or salt conditions, as well as water and metabolites conduction and translocation toward fruit. In contrast, rapid and negative responses of most of the ClNACs to low-temperature adversity may be related to the sensitivity to cold stress. Crosstalks among these abiotic stresses and hormone (abscisic acid and jasmonic acid) pathways were also discussed based on the expression of ClNAC genes. Our results will provide useful insights for the functional mining of NAC family in watermelon, as well as into the mechanisms underlying abiotic tolerance in other cash crops.

  2. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-01-01

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail. PMID:22796650

  3. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors.

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-09-15

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail.

  4. Genomic analyses and transcriptional profiles of the glycoside hydrolase family 18 genes of the entomopathogenic fungus Metarhizium anisopliae.

    Science.gov (United States)

    Junges, Ângela; Boldo, Juliano Tomazzoni; Souza, Bárbara Kunzler; Guedes, Rafael Lucas Muniz; Sbaraini, Nicolau; Kmetzsch, Lívia; Thompson, Claudia Elizabeth; Staats, Charley Christian; de Almeida, Luis Gonzaga Paula; de Vasconcelos, Ana Tereza Ribeiro; Vainstein, Marilene Henning; Schrank, Augusto

    2014-01-01

    Fungal chitin metabolism involves diverse processes such as metabolically active cell wall maintenance, basic nutrition, and different aspects of virulence. Chitinases are enzymes belonging to the glycoside hydrolase family 18 (GH18) and 19 (GH19) and are responsible for the hydrolysis of β-1,4-linkages in chitin. This linear homopolymer of N-acetyl-β-D-glucosamine is an essential constituent of fungal cell walls and arthropod exoskeletons. Several chitinases have been directly implicated in structural, morphogenetic, autolytic and nutritional activities of fungal cells. In the entomopathogen Metarhizium anisopliae, chitinases are also involved in virulence. Filamentous fungi genomes exhibit a higher number of chitinase-coding genes than bacteria or yeasts. The survey performed in the M. anisopliae genome has successfully identified 24 genes belonging to glycoside hydrolase family 18, including three previously experimentally determined chitinase-coding genes named chit1, chi2 and chi3. These putative chitinases were classified based on domain organization and phylogenetic analysis into the previously described A, B and C chitinase subgroups, and into a new subgroup D. Moreover, three GH18 proteins could be classified as putative endo-N-acetyl-β-D-glucosaminidases, enzymes that are associated with deglycosylation and were therefore assigned to a new subgroup E. The transcriptional profile of the GH18 genes was evaluated by qPCR with RNA extracted from eight culture conditions, representing different stages of development or different nutritional states. The transcripts from the GH18 genes were detected in at least one of the different M. anisopliae developmental stages, thus validating the proposed genes. Moreover, not all members from the same chitinase subgroup presented equal patterns of transcript expression under the eight distinct conditions studied. The determination of M. anisopliae chitinases and ENGases and a more detailed study concerning the enzymes

  5. Genomic analyses and transcriptional profiles of the glycoside hydrolase family 18 genes of the entomopathogenic fungus Metarhizium anisopliae.

    Directory of Open Access Journals (Sweden)

    Ângela Junges

    Full Text Available Fungal chitin metabolism involves diverse processes such as metabolically active cell wall maintenance, basic nutrition, and different aspects of virulence. Chitinases are enzymes belonging to the glycoside hydrolase family 18 (GH18 and 19 (GH19 and are responsible for the hydrolysis of β-1,4-linkages in chitin. This linear homopolymer of N-acetyl-β-D-glucosamine is an essential constituent of fungal cell walls and arthropod exoskeletons. Several chitinases have been directly implicated in structural, morphogenetic, autolytic and nutritional activities of fungal cells. In the entomopathogen Metarhizium anisopliae, chitinases are also involved in virulence. Filamentous fungi genomes exhibit a higher number of chitinase-coding genes than bacteria or yeasts. The survey performed in the M. anisopliae genome has successfully identified 24 genes belonging to glycoside hydrolase family 18, including three previously experimentally determined chitinase-coding genes named chit1, chi2 and chi3. These putative chitinases were classified based on domain organization and phylogenetic analysis into the previously described A, B and C chitinase subgroups, and into a new subgroup D. Moreover, three GH18 proteins could be classified as putative endo-N-acetyl-β-D-glucosaminidases, enzymes that are associated with deglycosylation and were therefore assigned to a new subgroup E. The transcriptional profile of the GH18 genes was evaluated by qPCR with RNA extracted from eight culture conditions, representing different stages of development or different nutritional states. The transcripts from the GH18 genes were detected in at least one of the different M. anisopliae developmental stages, thus validating the proposed genes. Moreover, not all members from the same chitinase subgroup presented equal patterns of transcript expression under the eight distinct conditions studied. The determination of M. anisopliae chitinases and ENGases and a more detailed study

  6. Transcription analysis of the major antigenic protein 1 multigene family of three in vitro-cultured Ehrlichia ruminantium isolates.

    Science.gov (United States)

    Bekker, Cornelis P J; Postigo, Milagros; Taoufik, Amar; Bell-Sakyi, Lesley; Ferraz, Conchita; Martinez, Dominique; Jongejan, Frans

    2005-07-01

    Ehrlichia ruminantium, an obligate intracellular bacterium transmitted by ticks of the genus Amblyomma, causes heartwater disease in ruminants. The gene coding for the major antigenic protein MAP1 is part of a multigene family consisting of a cluster containing 16 paralogs. In the search for differentially regulated genes between E. ruminantium grown in endothelial and tick cell lines that could be used in vaccine development and to determine if differences in the map1 gene cluster exist between different isolates of E. ruminantium, we analyzed the map1 gene cluster of the Senegal and Gardel isolates of E. ruminantium. Both isolates contained the same number of genes, and the same organization as found in the genome sequence of the Welgevonden isolate (H. Van Heerden, N. E. Collins, K. A. Brayton, C. Rademeyer, and B. A. Allsopp, Gene 330:159-168, 2004). However, comparison of two subpopulations of the Gardel isolate maintained in different laboratories demonstrated that recombination between map1-3 and map1-2 had occurred in one subpopulation with deletion of one entire gene. Reverse transcription-PCR on E. ruminantium derived mRNA from infected cells using gene-specific primers revealed that all 16 map1 paralogs were transcribed in endothelial cells. In one vector (Amblyomma variegatum) and several nonvector tick cell lines infected with E. ruminantium, transcripts were found for between 4 and 11 paralogs. In all these cases the transcript for the map1-1 gene was detected and was predominant. Our results indicate that the map1 gene cluster is relatively conserved but can be subject to recombination, and differences in the transcription of map1 multigenes in host and vector cell environments exist.

  7. The CesA gene family of barley. Quantitative analysis of transcripts reveals two groups of co-expressed genes.

    Science.gov (United States)

    Burton, Rachel A; Shirley, Neil J; King, Brendon J; Harvey, Andrew J; Fincher, Geoffrey B

    2004-01-01

    Sequence data from cDNA and genomic clones, coupled with analyses of expressed sequence tag databases, indicate that the CesA (cellulose synthase) gene family from barley (Hordeum vulgare) has at least eight members, which are distributed across the genome. Quantitative polymerase chain reaction has been used to determine the relative abundance of mRNA transcripts for individual HvCesA genes in vegetative and floral tissues, at different stages of development. To ensure accurate expression profiling, geometric averaging of multiple internal control gene transcripts has been applied for the normalization of transcript abundance. Total HvCesA mRNA levels are highest in coleoptiles, roots, and stems and much lower in floral tissues, early developing grain, and in the elongation zone of leaves. In most tissues, HvCesA1, HvCesA2, and HvCesA6 predominate, and their relative abundance is very similar; these genes appear to be coordinately transcribed. A second group, comprising HvCesA4, HvCesA7, and HvCesA8, also appears to be coordinately transcribed, most obviously in maturing stem and root tissues. The HvCesA3 expression pattern does not fall into either of these two groups, and HvCesA5 transcript levels are extremely low in all tissues. Thus, the HvCesA genes fall into two general groups of three genes with respect to mRNA abundance, and the co-expression of the groups identifies their products as candidates for the rosettes that are involved in cellulose biosynthesis at the plasma membrane. Phylogenetic analysis allows the two groups of genes to be linked with orthologous Arabidopsis CesA genes that have been implicated in primary and secondary wall synthesis.

  8. Members of the CREB/ATF and AP1 family of transcription factors are involved in the regulation of SOX18 gene expression

    Directory of Open Access Journals (Sweden)

    Petrović Isidora

    2011-01-01

    Full Text Available The SOX18 transcription factor plays an important role in endothelial cell specification, angiogenesis and atherogenesis. By profiling transcription factor interactions (TranSignal TM TF Protein Array we identified several transcription factors implicated in angiogenesis that have the ability to bind to the SOX18 optimal promoter region in vitro. In this report we focused our attention on distinct transcription factors identified by the array as belonging to AP-1 and CREB/ATF protein families. In particular, we analyzed the effects of CREB, JunB, c-Jun and ATF3 on SOX18 gene expression. Functional analysis revealed that CREB acts as a repressor, while JunB, c-Jun and ATF3 act as activators of SOX18 promoter activity. Our findings indicate that a transcriptional network that includes CREB, JunB, c-Jun and ATF3 could be involved in angiogenesis-related transcriptional regulation of the SOX18 gene.

  9. Evolutionary expansion and divergence in a large family of primate-specific zinc finger transcription factor genes

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, A T; Huntley, S; Tran-Gyamfi, M; Baggott, D; Gordon, L; Stubbs, L

    2005-09-28

    Although most genes are conserved as one-to-one orthologs in different mammalian orders, certain gene families have evolved to comprise different numbers and types of protein-coding genes through independent series of gene duplications, divergence and gene loss in each evolutionary lineage. One such family encodes KRAB-zinc finger (KRAB-ZNF) genes, which are likely to function as transcriptional repressors. One KRAB-ZNF subfamily, the ZNF91 clade, has expanded specifically in primates to comprise more than 110 loci in the human genome, yielding large gene clusters in human chromosomes 19 and 7 and smaller clusters or isolated copies at other chromosomal locations. Although phylogenetic analysis indicates that many of these genes arose before the split between old world monkeys and new world monkeys, the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. The paralogous loci are distinguished by sequence divergence within their zinc finger arrays indicating a selection for proteins with different DNA binding specificities. RT-PCR and in situ hybridization data show that some of these ZNF genes can have tissue-specific expression patterns, however many KRAB-ZNFs that are near-ubiquitous could also be playing very specific roles in halting target pathways in all tissues except for a few, where the target is released by the absence of its repressor. The number of variant KRAB-ZNF proteins is increased not only because of the large number of loci, but also because many loci can produce multiple splice variants, which because of the modular structure of these genes may have separate and perhaps even conflicting regulatory roles. The lineage-specific duplication and rapid divergence of this family of transcription factor genes suggests a role in determining species-specific biological differences and the evolution of novel primate traits.

  10. Positioning the expanded akirin gene family of Atlantic salmon within the transcriptional networks of myogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Macqueen, Daniel J., E-mail: djm59@st-andrews.ac.uk [Laboratory of Physiological and Evolutionary Genomics, Scottish Oceans Institute, University of St Andrews, St Andrews, Fife KY16 8LB (United Kingdom); Bower, Neil I., E-mail: nib@st-andrews.ac.uk [Laboratory of Physiological and Evolutionary Genomics, Scottish Oceans Institute, University of St Andrews, St Andrews, Fife KY16 8LB (United Kingdom); Johnston, Ian A., E-mail: iaj@st-andrews.ac.uk [Laboratory of Physiological and Evolutionary Genomics, Scottish Oceans Institute, University of St Andrews, St Andrews, Fife KY16 8LB (United Kingdom)

    2010-10-01

    Research highlights: {yields} The expanded akirin gene family of Atlantic salmon was characterised. {yields} akirin paralogues are regulated between mono- and multi-nucleated muscle cells. {yields} akirin paralogues positioned within known genetic networks controlling myogenesis. {yields} Co-expression of akirin paralogues is evident across cell types/during myogenesis. {yields} Selection has likely maintained common regulatory elements among akirin paralogues. -- Abstract: Vertebrate akirin genes usually form a family with one-to-three members that regulate gene expression during the innate immune response, carcinogenesis and myogenesis. We recently established that an expanded family of eight akirin genes is conserved across salmonid fish. Here, we measured mRNA levels of the akirin family of Atlantic salmon (Salmo salar L.) during the differentiation of primary myoblasts cultured from fast-skeletal muscle. Using hierarchical clustering and correlation, the data was positioned into a network of expression profiles including twenty further genes that regulate myogenesis. akirin1(2b) was not significantly regulated during the maturation of the cell culture. akirin2(1a) and 2(1b), along with IGF-II and several igfbps, were most highly expressed in mononuclear cells, then significantly and constitutively downregulated as differentiation proceeded and myotubes formed/matured. Conversely, akirin1(1a), 1(1b), 1(2a), 2(2a) and 2(2b) were expressed at lowest levels when mononuclear cells dominated the culture and highest levels when confluent layers of myotubes were evident. However, akirin1(2a) and 2(2a) were first upregulated earlier than akirin1(1a), 1(1b) and 2(2b), when rates of myoblast proliferation were highest. Interestingly, akirin1(1b), 1(2a), 2(2a) and 2(2b) formed part of a module of co-expressed genes involved in muscle differentiation, including myod1a, myog, mef2a, 14-3-3{beta} and 14-3-3{gamma}. All akirin paralogues were expressed ubiquitously across ten

  11. Genome-Wide Dissection of the Heat Shock Transcription Factor Family Genes in Arachis.

    Science.gov (United States)

    Wang, Pengfei; Song, Hui; Li, Changsheng; Li, Pengcheng; Li, Aiqin; Guan, Hongshan; Hou, Lei; Wang, Xingjun

    2017-01-01

    Heat shock transcription factors (Hsfs) are important transcription factors (TFs) in protecting plants from damages caused by various stresses. The released whole genome sequences of wild peanuts make it possible for genome-wide analysis of Hsfs in peanut. In this study, a total of 16 and 17 Hsf genes were identified from Arachis duranensis and A. ipaensis, respectively. We identified 16 orthologous Hsf gene pairs in both peanut species; however HsfXs was only identified from A. ipaensis. Orthologous pairs between two wild peanut species were highly syntenic. Based on phylogenetic relationship, peanut Hsfs were divided into groups A, B, and C. Selection pressure analysis showed that group B Hsf genes mainly underwent positive selection and group A Hsfs were affected by purifying selection. Small scale segmental and tandem duplication may play important roles in the evolution of these genes. Cis-elements, such as ABRE, DRE, and HSE, were found in the promoters of most Arachis Hsf genes. Five AdHsfs and two AiHsfs contained fungal elicitor responsive elements suggesting their involvement in response to fungi infection. These genes were differentially expressed in cultivated peanut under abiotic stress and Aspergillus flavus infection. AhHsf2 and AhHsf14 were significantly up-regulated after inoculation with A. flavus suggesting their possible role in fungal resistance.

  12. Erythroid cell-specific alpha-globin gene regulation by the CP2 transcription factor family.

    Science.gov (United States)

    Kang, Ho Chul; Chae, Ji Hyung; Lee, Yeon Ho; Park, Mi-Ae; Shin, June Ho; Kim, Sung-Hyun; Ye, Sang-Kyu; Cho, Yoon Shin; Fiering, Steven; Kim, Chul Geun

    2005-07-01

    We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of alpha-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of alpha-globin occurred following dimerization between CP2b and CP2c in erythroid K562 and MEL cells, but this dimerization did not activate the alpha-globin promoter in nonerythroid 293T cells, indicating that an additional erythroid factor is missing in 293T cells. PIAS1 was confirmed as a CP2 binding protein by the yeast two-hybrid screen, and expression of CP2b, CP2c, and PIAS1 in 293T cell induced alpha-globin promoter activation. These results show that ubiquitously expressed CP2b exerts potent erythroid cell-specific alpha-globin gene expression by complexing with CP2c and PIAS1.

  13. Erythroid Cell-Specific α-Globin Gene Regulation by the CP2 Transcription Factor Family

    Science.gov (United States)

    Kang, Ho Chul; Chae, Ji Hyung; Lee, Yeon Ho; Park, Mi-Ae; Shin, June Ho; Kim, Sung-Hyun; Ye, Sang-Kyu; Cho, Yoon Shin; Fiering, Steven; Kim, Chul Geun

    2005-01-01

    We previously demonstrated that ubiquitously expressed CP2c exerts potent erythroid-specific transactivation of α-globin through an unknown mechanism. This mechanism is reported here to involve specific CP2 splice variants and protein inhibitor of activated STAT1 (PIAS1). We identify a novel murine splice isoform of CP2, CP2b, which is identical to CP2a except that it has an additional 36 amino acids encoded by an extra exon. CP2b has an erythroid cell-specific transcriptional activation domain, which requires the extra exon and can form heteromeric complexes with other CP2 isoforms, but lacks the DNA binding activity found in CP2a and CP2c. Transcriptional activation of α-globin occurred following dimerization between CP2b and CP2c in erythroid K562 and MEL cells, but this dimerization did not activate the α-globin promoter in nonerythroid 293T cells, indicating that an additional erythroid factor is missing in 293T cells. PIAS1 was confirmed as a CP2 binding protein by the yeast two-hybrid screen, and expression of CP2b, CP2c, and PIAS1 in 293T cell induced α-globin promoter activation. These results show that ubiquitously expressed CP2b exerts potent erythroid cell-specific α-globin gene expression by complexing with CP2c and PIAS1. PMID:15988015

  14. Transcriptome-wide identification and expression profiling of the DOF transcription factor gene family in Chrysanthemum morifolium

    Directory of Open Access Journals (Sweden)

    Aiping eSong

    2016-02-01

    Full Text Available The family of DNA binding with one finger (DOF transcription factors is plant specific, and these proteins contain a highly conserved domain (DOF domain of 50-52 amino acids that includes a C2C2-type zinc finger motif at the N-terminus that is known to function in a number of plant processes. Here, we characterized 20 DOF genes in the important ornamental species chrysanthemum (Chrysanthemum morifolium based on transcriptomic sequences. Phylogenetic analysis identified one pair of putative orthologous proteins in Arabidopsis and chrysanthemum and six pairs of paralogous proteins in chrysanthemum. Conserved motifs in the DOF proteins shared by Arabidopsis and chrysanthemum were analysed using MEME. Bioinformatics analysis revealed that 13 CmDOFs could be targeted by 16 miRNA families. Moreover, we used 5’ RLM-RACE to map the cleavage sites in CmDOF3, 15 and 21. The expression of these 20 genes in response to phytohormone treatments and abiotic stresses was characterized, and the expression patterns of six pairs of paralogous CmDOF genes were found to completely differ from one another, except for CmDOF6 and CmDOF7. This work will promote our research of the various functions of DOF gene family members in plant hormone and stress responses.

  15. Gene Structures, Evolution and Transcriptional Profiling of the WRKY Gene Family in Castor Bean (Ricinus communis L..

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    Zhi Zou

    Full Text Available WRKY proteins comprise one of the largest transcription factor families in plants and form key regulators of many plant processes. This study presents the characterization of 58 WRKY genes from the castor bean (Ricinus communis L., Euphorbiaceae genome. Compared with the automatic genome annotation, one more WRKY-encoding locus was identified and 20 out of the 57 predicted gene models were manually corrected. All RcWRKY genes were shown to contain at least one intron in their coding sequences. According to the structural features of the present WRKY domains, the identified RcWRKY genes were assigned to three previously defined groups (I-III. Although castor bean underwent no recent whole-genome duplication event like physic nut (Jatropha curcas L., Euphorbiaceae, comparative genomics analysis indicated that one gene loss, one intron loss and one recent proximal duplication occurred in the RcWRKY gene family. The expression of all 58 RcWRKY genes was supported by ESTs and/or RNA sequencing reads derived from roots, leaves, flowers, seeds and endosperms. Further global expression profiles with RNA sequencing data revealed diverse expression patterns among various tissues. Results obtained from this study not only provide valuable information for future functional analysis and utilization of the castor bean WRKY genes, but also provide a useful reference to investigate the gene family expansion and evolution in Euphorbiaceus plants.

  16. Gene Structures, Evolution and Transcriptional Profiling of the WRKY Gene Family in Castor Bean (Ricinus communis L.).

    Science.gov (United States)

    Zou, Zhi; Yang, Lifu; Wang, Danhua; Huang, Qixing; Mo, Yeyong; Xie, Guishui

    2016-01-01

    WRKY proteins comprise one of the largest transcription factor families in plants and form key regulators of many plant processes. This study presents the characterization of 58 WRKY genes from the castor bean (Ricinus communis L., Euphorbiaceae) genome. Compared with the automatic genome annotation, one more WRKY-encoding locus was identified and 20 out of the 57 predicted gene models were manually corrected. All RcWRKY genes were shown to contain at least one intron in their coding sequences. According to the structural features of the present WRKY domains, the identified RcWRKY genes were assigned to three previously defined groups (I-III). Although castor bean underwent no recent whole-genome duplication event like physic nut (Jatropha curcas L., Euphorbiaceae), comparative genomics analysis indicated that one gene loss, one intron loss and one recent proximal duplication occurred in the RcWRKY gene family. The expression of all 58 RcWRKY genes was supported by ESTs and/or RNA sequencing reads derived from roots, leaves, flowers, seeds and endosperms. Further global expression profiles with RNA sequencing data revealed diverse expression patterns among various tissues. Results obtained from this study not only provide valuable information for future functional analysis and utilization of the castor bean WRKY genes, but also provide a useful reference to investigate the gene family expansion and evolution in Euphorbiaceus plants.

  17. Biophysical analysis of MarR family transcription factors from Streptomyces coelicolor

    OpenAIRE

    Holley, Tracey

    2012-01-01

    Streptomycetes represent a rich source of potentially useful therapeutics. However, in a laboratory environment, a large proportion of their secondary metabolite gene clusters remain silent, and thus their full metabolic potential is not realised. One way to unlock these so-called "cryptic" clusters may be to manipulate specific regulatory proteins. But, the vast majority of these regulators are uncharacterized, making it difficult to do this in a rational way. The MarR family of regulatory p...

  18. Transcriptional regulation by VirR and VirS of members of the Rhodococcus equi virulence-associated protein multigene family.

    Science.gov (United States)

    Kakuda, Tsutomu; Miyazaki, Shiko; Hagiuda, Hirofumi; Takai, Shinji

    2015-08-01

    A virulence plasmid of Rhodococcus equi harbors the vap mutigene family. Here it is shown that transcription of vap gene family members other than vapA (vapD, vapE and vapG) is regulated by temperature and pH and abolished when either virS or virR is deleted. Expression of VirS in the absence of functional VirR was found to increase the transcription of vap genes to the amount expressed in the presence of VirR. These findings suggest that transcription of vap genes is regulated by VirS and that VirR is involved in the mechanism of transcriptional responses to temperature and pH. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.

  19. The role of Zic family zinc finger transcription factors in the proliferation and differentiation of retinal progenitor cells

    Energy Technology Data Exchange (ETDEWEB)

    Watabe, Yui [Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo (Japan); Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Division of Orthoptics, Teikyo University School of Medical Care and Technology, Tokyo (Japan); Baba, Yukihiro [Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo (Japan); Nakauchi, Hiromitsu [Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyo (Japan); Mizota, Atsushi [Department of Ophthalmology, Teikyo University School of Medicine, Tokyo (Japan); Watanabe, Sumiko, E-mail: sumiko@ims.u-tokyo.ac.jp [Division of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo (Japan)

    2011-11-11

    Highlights: Black-Right-Pointing-Pointer Zic transcription factors expressed early retinal progenitor cells. Black-Right-Pointing-Pointer Zics sustain proliferation activity of retinal progenitor cells. Black-Right-Pointing-Pointer Overexpression of Zic in retinal progenitors perturbed rod differentiation. Black-Right-Pointing-Pointer Fate determination to rod photoreceptor was not affected. -- Abstract: Members of the Zic family of zinc finger transcription factors play critical roles in a variety of developmental processes. Using DNA microarray analysis, we found that Zics are strongly expressed in SSEA-1-positive early retinal progenitors in the peripheral region of the mouse retina. Reverse-transcription polymerase chain reaction using mRNA from the retina at various developmental stages showed that Zic1 and Zic2 are expressed in the embryonic retina and then gradually disappear during retinal development. Zic3 is also expressed in the embryonic retina; its expression level slightly decreases but it is expressed until adulthood. We overexpressed Zic1, Zic2, or Zic3 in retinal progenitors at embryonic day 17.5 and cultured the retina as explants for 2 weeks. The number of rod photoreceptors was fewer than in the control, but no other cell types showed significant differences between control and Zic overexpressing cells. The proliferation activity of normal retinal progenitors decreased after 5 days in culture, as observed in normal in vivo developmental processes. However, Zic expressing retinal cells continued to proliferate at days 5 and 7, suggesting that Zics sustain the proliferation activities of retinal progenitor cells. Since the effects of Zic1, 2, and 3 are indistinguishable in terms of differentiation and proliferation of retinal progenitors, the redundant function of Zics in retinal development is suggested.

  20. Genome-wide organization and expression profiling of the NAC transcription factor family in potato (Solanum tuberosum L.).

    Science.gov (United States)

    Singh, Anil Kumar; Sharma, Vishal; Pal, Awadhesh Kumar; Acharya, Vishal; Ahuja, Paramvir Singh

    2013-08-01

    NAC [no apical meristem (NAM), Arabidopsis thaliana transcription activation factor [ATAF1/2] and cup-shaped cotyledon (CUC2)] proteins belong to one of the largest plant-specific transcription factor (TF) families and play important roles in plant development processes, response to biotic and abiotic cues and hormone signalling. Our genome-wide analysis identified 110 StNAC genes in potato encoding for 136 proteins, including 14 membrane-bound TFs. The physical map positions of StNAC genes on 12 potato chromosomes were non-random, and 40 genes were found to be distributed in 16 clusters. The StNAC proteins were phylogenetically clustered into 12 subgroups. Phylogenetic analysis of StNACs along with their Arabidopsis and rice counterparts divided these proteins into 18 subgroups. Our comparative analysis has also identified 36 putative TNAC proteins, which appear to be restricted to Solanaceae family. In silico expression analysis, using Illumina RNA-seq transcriptome data, revealed tissue-specific, biotic, abiotic stress and hormone-responsive expression profile of StNAC genes. Several StNAC genes, including StNAC072 and StNAC101that are orthologs of known stress-responsive Arabidopsis RESPONSIVE TO DEHYDRATION 26 (RD26) were identified as highly abiotic stress responsive. Quantitative real-time polymerase chain reaction analysis largely corroborated the expression profile of StNAC genes as revealed by the RNA-seq data. Taken together, this analysis indicates towards putative functions of several StNAC TFs, which will provide blue-print for their functional characterization and utilization in potato improvement.

  1. A novel TetR family transcriptional regulator, SAV576, negatively controls avermectin biosynthesis in Streptomyces avermitilis.

    Science.gov (United States)

    Guo, Jia; Zhang, Xuan; Luo, Shuai; He, Fei; Chen, Zhi; Wen, Ying; Li, Jilun

    2013-01-01

    Avermectins produced by Streptomyces avermitilis are potent anti-parasitic agents that are useful in animal health care, agriculture, and the treatment of human infections. In a search for novel regulators that affect avermectin biosynthesis, comparative transcriptome analysis was performed between wild-type strain ATCC31267 and avermectin overproducing strain 76-02-e, revealing some differentially expressed genes. SAV576, which is downregulated in 76-02-e and encodes a TetR family transcriptional regulator (TFR), was shown to inhibit avermectin production by indirectly affecting the expression of ave genes. SAV576 directly repressed the transcription of its gene SAV576 and of adjacent genes SAV575 (encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and SAV574. The SAV576-binding sites within the bidirectional SAV575-SAV576 promoter region were determined by DNase I footprinting assays. A consensus 15-bp palindromic sequence CCRTACRVYGTATGS was found in these binding sites and shown to be important for SAV576-binding activity. SAV575, an important target gene of SAV576, was shown to exert a positive effect on avermectin production. The study findings extend our limited knowledge of the complex regulation of avermectin biosynthesis and provide a basis for rational genetic manipulation of S. avermitilis to improve avermectin production through control of SAV576 and its target gene.

  2. A novel TetR family transcriptional regulator, SAV576, negatively controls avermectin biosynthesis in Streptomyces avermitilis.

    Directory of Open Access Journals (Sweden)

    Jia Guo

    Full Text Available Avermectins produced by Streptomyces avermitilis are potent anti-parasitic agents that are useful in animal health care, agriculture, and the treatment of human infections. In a search for novel regulators that affect avermectin biosynthesis, comparative transcriptome analysis was performed between wild-type strain ATCC31267 and avermectin overproducing strain 76-02-e, revealing some differentially expressed genes. SAV576, which is downregulated in 76-02-e and encodes a TetR family transcriptional regulator (TFR, was shown to inhibit avermectin production by indirectly affecting the expression of ave genes. SAV576 directly repressed the transcription of its gene SAV576 and of adjacent genes SAV575 (encodes cytochrome P450/NADPH-ferrihemoprotein reductase and SAV574. The SAV576-binding sites within the bidirectional SAV575-SAV576 promoter region were determined by DNase I footprinting assays. A consensus 15-bp palindromic sequence CCRTACRVYGTATGS was found in these binding sites and shown to be important for SAV576-binding activity. SAV575, an important target gene of SAV576, was shown to exert a positive effect on avermectin production. The study findings extend our limited knowledge of the complex regulation of avermectin biosynthesis and provide a basis for rational genetic manipulation of S. avermitilis to improve avermectin production through control of SAV576 and its target gene.

  3. A new perspective on the role of the CREB family of transcription factors in memory consolidation via adult hippocampal neurogenesis

    Directory of Open Access Journals (Sweden)

    Sylvia eOrtega-Martinez

    2015-08-01

    Full Text Available Adult neurogenesis is the process by which new neurons are generated in the brains of adults. Since its discovery 50 years ago, adult neurogenesis has been widely studied in the mammalian brain and has provided a new perspective on the pathophysiology of many psychiatric and neurodegenerative disorders, some of which affect memory. In this regard, adult hippocampal neurogenesis (AHN, which occurs in the subgranular zone of the dentate gyrus, has been suggested to play a role in the formation and consolidation of new memories. This process involves many transcription factors, of which cyclic AMP-responsive element-binding protein (CREB is a well-documented one. In the developing brain, CREB regulates crucial cell stages, (e.g., proliferation, differentiation, and survival, and in the adult brain, it participates in neuronal plasticity, learning, and memory. In addition, new evidence supports the hypothesis that CREB may also participate in learning and memory through its involvement in AHN. This review examines the CREB family of transcription factors, including the different members and known signaling pathways. It highlights the role of CREB as a modulator of AHN, which could underlie its function in memory consolidation mechanisms.

  4. Distinct Roles for Interfacial Hydration in Site-Specific DNA Recognition by ETS-Family Transcription Factors.

    Science.gov (United States)

    Xhani, Suela; Esaki, Shingo; Huang, Kenneth; Erlitzki, Noa; Poon, Gregory M K

    2017-04-06

    The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. Unlike other ETS homologues, such as Ets-1, DNA recognition by PU.1 is highly sensitive to its osmotic environment due to excess interfacial hydration in the complex. To investigate interfacial hydration in the two homologues, we mutated a conserved tyrosine residue, which is exclusively engaged in coordinating a well-defined water contact between the protein and DNA among ETS proteins, to phenylalanine. The loss of this water-mediated contact blunted the osmotic sensitivity of PU.1/DNA binding, but did not alter binding under normo-osmotic conditions, suggesting that PU.1 has evolved to maximize osmotic sensitivity. The homologous mutation in Ets-1, which was minimally sensitive to osmotic stress due to a sparsely hydrated interface, reduced DNA-binding affinity at normal osmolality but the complex became stabilized by osmotic stress. Molecular dynamics simulations of wildtype and mutant PU.1 and Ets-1 in their free and DNA-bound states, which recapitulated experimental features of the proteins, showed that abrogation of this tyrosine-mediated water contact perturbed the Ets-1/DNA complex not through disruption of interfacial hydration, but by inhibiting local dynamics induced specifically in the bound state. Thus, a configurationally identical water-mediated contact plays mechanistically distinct roles in mediating DNA recognition by structurally homologous ETS transcription factors.

  5. Evolution and Functional Diversification of the GLI Family of Transcription Factors in Vertebrates

    Directory of Open Access Journals (Sweden)

    Amir Ali Abbasi

    2009-01-01

    Full Text Available Background: In vertebrates the “SONIC HEDGEHOG” signalling pathway has been implicated in cell-fate determination, proliferation and the patterning of many different cell types and organs. As the GLI family members (GLI1, GLI2 and GLI3 are key mediators of hedgehog morphogenetic signals, over the past couple of decades they have been extensively scrutinized by genetic, molecular and biochemical means. Thus, a great deal of information is currently available about the functional aspects of GLI proteins in various vertebrate species. To address the roles of GLI genes in diversifying the repertoire of the Hh signalling and deploying them for the vertebrate specifications, in this study we have examined the evolutionary patterns of vertebrate GLI sequences within and between species.Results: Phylogenetic tree analysis suggests that the vertebrate GLI1, GLI2 and GLI3 genes diverged after the separation of urochordates from vertebrates and before the tetrapods-bony fishes split. Lineage specific duplication events were also detected. Estimation of mode and strength of selection acting on GLI orthologs demonstrated that all members of the GLI gene family experienced more relaxed selection in teleost fish than in the mammalian lineage. Furthermore, the GLI1 gene appeared to have been exposed to different functional constraints in fish and tetrapod lineages, whilst a similar level of functional constraints on GLI2 and GLI3 was suggested by comparable average non-synonymous (Ka substitutions across the lineages. A relative rate test suggested that the majority of the paralogous copies of the GLI family analyzed evolved with similar evolutionary rates except GLI1 which evolved at a significantly faster rate than its paralogous counterparts in tetrapods.Conclusions: Our analysis shows that sequence evolutionary patterns of GLI family members are largely correlated with the reported similarities and differences in the functionality of GLI proteins within

  6. Evolution and Functional Diversification of the GLI Family of Transcription Factors in Vertebrates

    Directory of Open Access Journals (Sweden)

    Amir Ali Abbasi

    2009-05-01

    Full Text Available Background: In vertebrates the “SONIC HEDGEHOG” signalling pathway has been implicated in cell-fate determination, proliferation and the patterning of many different cell types and organs. As the GLI family members (GLI1, GLI2 and GLI3 are key mediators of hedgehog morphogenetic signals, over the past couple of decades they have been extensively scrutinized by genetic, molecular and biochemical means. Thus, a great deal of information is currently available about the functional aspects of GLI proteins in various vertebrate species. To address the roles of GLI genes in diversifying the repertoire of the Hh signalling and deploying them for the vertebrate specifications, in this study we have examined the evolutionary patterns of vertebrate GLI sequences within and between species. Results: Phylogenetic tree analysis suggests that the vertebrate GLI1, GLI2 and GLI3 genes diverged after the separation of urochordates from vertebrates and before the tetrapods-bony fishes split. Lineage specific duplication events were also detected. Estimation of mode and strength of selection acting on GLI orthologs demonstrated that all members of the GLI gene family experienced more relaxed selection in teleost fish than in the mammalian lineage. Furthermore, the GLI1 gene appeared to have been exposed to different functional constraints in fish and tetrapod lineages, whilst a similar level of functional constraints on GLI2 and GLI3 was suggested by comparable average non-synonymous (Ka substitutions across the lineages. A relative rate test suggested that the majority of the paralogous copies of the GLI family analyzed evolved with similar evolutionary rates except GLI1 which evolved at a significantly faster rate than its paralogous counterparts in tetrapods. Conclusions: Our analysis shows that sequence evolutionary patterns of GLI family members are largely correlated with the reported similarities and differences in the functionality of GLI proteins

  7. ICAT Inhibits beta-Catenin Binding to Tcf/Lef-Family Transcription Factors and in the General Coactivator p300 Using Independent Structural Modules

    Energy Technology Data Exchange (ETDEWEB)

    Daniels, D. L.

    2002-01-01

    In the canonical Wnt signaling pathway, {beta}-catenin activates target genes through its interactions with Tcf/Lef-family transcription factors and additional transcriptional coactivators. The crystal structure of ICAT, an inhibitor of {beta}-catenin-mediated transcription, bound to the armadillo repeat domain of {beta}-catenin, has been determined. ICAT contains an N-terminal helilical domain that binds to repeats 11 and 12 of {beta}-catenin, and an extended C-terminal region that binds to repeats 5-10 in a manner similar that of Tcfs and other {beta}-catenin ligands. Full-length ICAT dissociates complexes of {beta}-catenin, Lef-1, and the transcriptional coactivator p300, whereas the helical domain alone selectively blocks binding to p300. The C-terminal armadillo repeats of {beta}-catenin may be an attractive target for compounds designed to disrupt aberrant {beta}-catenin-mediated transcription associated with various cancers.

  8. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins.

    Science.gov (United States)

    Vilas, Jéssica M; Ferreirós, Alba; Carneiro, Carmen; Morey, Lluis; Da Silva-Álvarez, Sabela; Fernandes, Tânia; Abad, María; Di Croce, Luciano; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-02-20

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression.

  9. Transcriptional regulation of Sox2 by the retinoblastoma family of pocket proteins

    Science.gov (United States)

    Carneiro, Carmen; Morey, Lluis; Silva-Álvarez, Sabela Da; Fernandes, Tânia; Abad, María; Croce, Luciano Di; García-Caballero, Tomás; Serrano, Manuel; Rivas, Carmen; Vidal, Anxo; Collado, Manuel

    2015-01-01

    Cellular reprogramming to iPSCs has uncovered unsuspected links between tumor suppressors and pluripotency factors. Using this system, it was possible to identify tumor suppressor p27 as a repressor of Sox2 during differentiation. This led to the demonstration that defects in the repression of Sox2 can contribute to tumor development. The members of the retinoblastoma family of pocket proteins, pRb, p107 and p130, are negative regulators of the cell cycle with tumor suppressor activity and with roles in differentiation. In this work we studied the relative contribution of the retinoblastoma family members to the regulation of Sox2 expression. We found that deletion of Rb or p130 leads to impaired repression of Sox2, a deffect amplified by inactivation of p53. We also identified binding of pRb and p130 to an enhancer with crucial regulatory activity on Sox2 expression. Using cellular reprogramming we tested the impact of the defective repression of Sox2 and confirmed that Rb deficiency allows the generation of iPSCs in the absence of exogenous Sox2. Finally, partial depletion of Sox2 positive cells reduced the pituitary tumor development initiated by Rb loss in vivo. In summary, our results show that Sox2 repression by pRb is a relevant mechanism of tumor suppression. PMID:25576924

  10. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    Science.gov (United States)

    An, Shi-qi; Caly, Delphine L; McCarthy, Yvonne; Murdoch, Sarah L; Ward, Joseph; Febrer, Melanie; Dow, J Maxwell; Ryan, Robert P

    2014-10-01

    Bis-(3',5') cyclic di-guanylate (cyclic di-GMP) is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc). This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d)∼2 µM). Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  11. Novel cyclic di-GMP effectors of the YajQ protein family control bacterial virulence.

    Directory of Open Access Journals (Sweden)

    Shi-qi An

    2014-10-01

    Full Text Available Bis-(3',5' cyclic di-guanylate (cyclic di-GMP is a key bacterial second messenger that is implicated in the regulation of many critical processes that include motility, biofilm formation and virulence. Cyclic di-GMP influences diverse functions through interaction with a range of effectors. Our knowledge of these effectors and their different regulatory actions is far from complete, however. Here we have used an affinity pull-down assay using cyclic di-GMP-coupled magnetic beads to identify cyclic di-GMP binding proteins in the plant pathogen Xanthomonas campestris pv. campestris (Xcc. This analysis identified XC_3703, a protein of the YajQ family, as a potential cyclic di-GMP receptor. Isothermal titration calorimetry showed that the purified XC_3703 protein bound cyclic di-GMP with a high affinity (K(d∼2 µM. Mutation of XC_3703 led to reduced virulence of Xcc to plants and alteration in biofilm formation. Yeast two-hybrid and far-western analyses showed that XC_3703 was able to interact with XC_2801, a transcription factor of the LysR family. Mutation of XC_2801 and XC_3703 had partially overlapping effects on the transcriptome of Xcc, and both affected virulence. Electromobility shift assays showed that XC_3703 positively affected the binding of XC_2801 to the promoters of target virulence genes, an effect that was reversed by cyclic di-GMP. Genetic and functional analysis of YajQ family members from the human pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia showed that they also specifically bound cyclic di-GMP and contributed to virulence in model systems. The findings thus identify a new class of cyclic di-GMP effector that regulates bacterial virulence.

  12. Differential recognition of heat shock elements by members of the heat shock transcription factor family.

    Science.gov (United States)

    Yamamoto, Noritaka; Takemori, Yukiko; Sakurai, Mayumi; Sugiyama, Kazuhisa; Sakurai, Hiroshi

    2009-04-01

    Heat shock transcription factor (HSF), an evolutionarily conserved stress response regulator, forms trimers and binds to heat shock element (HSE), comprising at least three continuous inverted repeats of the sequence 5'-nGAAn-3'. The single HSF of yeast is also able to bind discontinuously arranged nGAAn units. We investigated interactions between three human HSFs and various HSE types in vitro, in yeast cells, and in HeLa cells. Human HSF1, a stress-activated regulator, preferentially bound to continuous HSEs rather than discontinuous HSEs, and heat shock of HeLa cells caused expression of reporter genes containing continuous HSEs. HSF2, whose function is implicated in neuronal specification and spermatogenesis, exhibited a slightly higher binding affinity to discontinuous HSEs than did HSF1. HSF4, a protein required for ocular lens development, efficiently recognized discontinuous HSEs in a trimerization-dependent manner. Among four human gamma-crystallin genes encoding structural proteins of the lens, heat-induced HSF1 preferred HSEs on the gammaA-crystallin and gammaB-crystallin promoters, whereas HSF4 preferred HSE on the gammaC-crystallin promoter. These results suggest that the HSE architecture is an important determinant of which HSF members regulate genes in diverse cellular processes.

  13. The BET Family of Proteins Targets Moloney Murine Leukemia Virus Integration near Transcription Start Sites

    Directory of Open Access Journals (Sweden)

    Jan De Rijck

    2013-11-01

    Full Text Available A hallmark of retroviral replication is integration of the viral genome into host cell DNA. This characteristic makes retrovirus-based vectors attractive delivery vehicles for gene therapy. However, adverse events in gene therapeutic trials, caused by activation of proto-oncogenes due to murine leukemia virus (MLV-derived vector integration, hamper their application. Here, we show that bromodomain and extraterminal (BET proteins (BRD2, BRD3, and BRD4 and MLV integrase specifically interact and colocalize within the nucleus of the cell. Inhibition of the BET proteins’ chromatin interaction via specific bromodomain inhibitors blocks MLV virus replication at the integration step. MLV integration site distribution parallels the chromatin binding profile of BET proteins, and expression of an artificial fusion protein of the BET integrase binding domain with the chromatin interaction domain of the lentiviral targeting factor LEDGF/p75 retargets MLV integration away from transcription start sites and into the body of actively transcribed genes, conforming to the HIV integration pattern. Together, these data validate BET proteins as MLV integration targeting factors.

  14. Structural basis of operator sites recognition and effector binding in the TetR family transcription regulator FadR.

    Science.gov (United States)

    Yeo, Hyun Ku; Park, Young Woo; Lee, Jae Young

    2017-04-20

    FadR is a fatty acyl-CoA dependent transcription factor that regulates genes encoding proteins involved in fatty-acid degradation and synthesis pathways. In this study, the crystal structures of Bacillus halodurans FadR, which belong to the TetR family, have been determined in three different forms: ligand-bound, ligand-free and DNA-bound at resolutions of 1.75, 2.05 and 2.80 Å, respectively. Structural and functional data showed that B. halodurans FadR was bound to its operator site without fatty acyl-CoAs. Structural comparisons among the three different forms of B. halodurans FadR revealed that the movement of DNA binding domains toward the operator DNA was blocked upon binding of ligand molecules. These findings suggest that the TetR family FadR negatively regulates the genes involved in fatty acid metabolism by binding cooperatively to the operator DNA as a dimer of dimers. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  15. Genome-wide analysis of the DNA-binding with one zinc finger (Dof) transcription factor family in bananas.

    Science.gov (United States)

    Dong, Chen; Hu, Huigang; Xie, Jianghui

    2016-12-01

    DNA-binding with one finger (Dof) domain proteins are a multigene family of plant-specific transcription factors involved in numerous aspects of plant growth and development. In this study, we report a genome-wide search for Musa acuminata Dof (MaDof) genes and their expression profiles at different developmental stages and in response to various abiotic stresses. In addition, a complete overview of the Dof gene family in bananas is presented, including the gene structures, chromosomal locations, cis-regulatory elements, conserved protein domains, and phylogenetic inferences. Based on the genome-wide analysis, we identified 74 full-length protein-coding MaDof genes unevenly distributed on 11 chromosomes. Phylogenetic analysis with Dof members from diverse plant species showed that MaDof genes can be classified into four subgroups (StDof I, II, III, and IV). The detailed genomic information of the MaDof gene homologs in the present study provides opportunities for functional analyses to unravel the exact role of the genes in plant growth and development.

  16. Genome-wide Identification of TCP Family Transcription Factors from Populus euphratica and Their Involvement in Leaf Shape Regulation.

    Science.gov (United States)

    Ma, Xiaodong; Ma, Jianchao; Fan, Di; Li, Chaofeng; Jiang, Yuanzhong; Luo, Keming

    2016-09-08

    Higher plants have been shown to experience a juvenile vegetative phase, an adult vegetative phase, and a reproductive phase during its postembryonic development and distinct lateral organ morphologies have been observed at the different development stages. Populus euphratica, commonly known as a desert poplar, has developed heteromorphic leaves during its development. The TCP family genes encode a group of plant-specific transcription factors involved in several aspects of plant development. In particular, TCPs have been shown to influence leaf size and shape in many herbaceous plants. However, whether these functions are conserved in woody plants remains unknown. In the present study, we carried out genome-wide identification of TCP genes in P. euphratica and P. trichocarpa, and 33 and 36 genes encoding putative TCP proteins were found, respectively. Phylogenetic analysis of the poplar TCPs together with Arabidopsis TCPs indicated a biased expansion of the TCP gene family via segmental duplications. In addition, our results have also shown a correlation between different expression patterns of several P. euphratica TCP genes and leaf shape variations, indicating their involvement in the regulation of leaf shape development.

  17. FBXO11 promotes ubiquitination of the Snail family of transcription factors in cancer progression and epidermal development

    Science.gov (United States)

    Jin, Yue; Shenoy, Anitha K.; Doernberg, Samuel; Chen, Hao; Luo, Huacheng; Shen, Huangxuan; Lin, Tong; Tarrash, Miriam; Cai, Qingsong; Hu, Xin; Fiske, Ryan; Chen, Ting; Wu, Lizi; Mohammed, Kamal A.; Rottiers, Veerle; Lee, Siu Sylvia; Lu, Jianrong

    2015-01-01

    The Snail family of transcription factors are core inducers of epithelial-to-mesenchymal transition (EMT). Here we show that the F-box protein FBXO11 recognizes and promotes ubiquitin-mediated degradation of multiple Snail family members including Scratch. The association between FBXO11 and Snai1 in vitro is independent of Snai1 phosphorylation. Overexpression of FBXO11 in mesenchymal cells reduces Snail protein abundance and cellular invasiveness. Conversely, depletion of endogenous FBXO11 in epithelial cancer cells causes Snail protein accumulation, EMT, and tumor invasion, as well as loss of estrogen receptor expression in breast cancer cells. Expression of FBXO11 is downregulated by EMT-inducing signals TGFβ and nickel. In human cancer, high FBXO11 levels correlate with expression of epithelial markers and favorable prognosis. The results suggest that FBXO11 sustains the epithelial state and inhibits cancer progression. Inactivation of FBXO11 in mice leads to neonatal lethality, epidermal thickening, and increased Snail protein levels in epidermis, validating that FBXO11 is a physiological ubiquitin ligase of Snail. Moreover, in C. elegans, the FBXO11 mutant phenotype is attributed to the Snail factors as it is suppressed by inactivation/depletion of Snail homologs. Collectively, these findings suggest that the FBXO11-Snail regulatory axis is evolutionarily conserved and critically governs carcinoma progression and mammalian epidermal development. PMID:25827072

  18. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Directory of Open Access Journals (Sweden)

    Xiao-Jin Hou

    Full Text Available MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB. Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  19. Genome-wide classification and evolutionary and expression analyses of citrus MYB transcription factor families in sweet orange.

    Science.gov (United States)

    Hou, Xiao-Jin; Li, Si-Bei; Liu, Sheng-Rui; Hu, Chun-Gen; Zhang, Jin-Zhi

    2014-01-01

    MYB family genes are widely distributed in plants and comprise one of the largest transcription factors involved in various developmental processes and defense responses of plants. To date, few MYB genes and little expression profiling have been reported for citrus. Here, we describe and classify 177 members of the sweet orange MYB gene (CsMYB) family in terms of their genomic gene structures and similarity to their putative Arabidopsis orthologs. According to these analyses, these CsMYBs were categorized into four groups (4R-MYB, 3R-MYB, 2R-MYB and 1R-MYB). Gene structure analysis revealed that 1R-MYB genes possess relatively more introns as compared with 2R-MYB genes. Investigation of their chromosomal localizations revealed that these CsMYBs are distributed across nine chromosomes. Sweet orange includes a relatively small number of MYB genes compared with the 198 members in Arabidopsis, presumably due to a paralog reduction related to repetitive sequence insertion into promoter and non-coding transcribed region of the genes. Comparative studies of CsMYBs and Arabidopsis showed that CsMYBs had fewer gene duplication events. Expression analysis revealed that the MYB gene family has a wide expression profile in sweet orange development and plays important roles in development and stress responses. In addition, 337 new putative microsatellites with flanking sequences sufficient for primer design were also identified from the 177 CsMYBs. These results provide a useful reference for the selection of candidate MYB genes for cloning and further functional analysis forcitrus.

  20. Ixodes scapularis tick serine proteinase inhibitor (serpin gene family; annotation and transcriptional analysis

    Directory of Open Access Journals (Sweden)

    Chalaire Katelyn C

    2009-05-01

    Full Text Available Abstract Background Serine proteinase inhibitors (Serpins are a large superfamily of structurally related, but functionally diverse proteins that control essential proteolytic pathways in most branches of life. Given their importance in the biology of many organisms, the concept that ticks might utilize serpins to evade host defenses and immunizing against or disrupting their functions as targets for tick control is an appealing option. Results A sequence homology search strategy has allowed us to identify at least 45 tick serpin genes in the Ixodes scapularis genome that are structurally segregated into 32 intronless and 13 intron-containing genes. Nine of the intron-containing serpins occur in a cluster of 11 genes that span 170 kb of DNA sequence. Based on consensus amino acid residues in the reactive center loop (RCL and signal peptide scanning, 93% are putatively inhibitory while 82% are putatively extracellular. Among the 11 different amino acid residues that are predicted at the P1 sites, 16 sequences possess basic amino acid (R/K residues. Temporal and spatial expression analyses revealed that 40 of the 45 serpins are differentially expressed in salivary glands (SG and/or midguts (MG of unfed and partially fed ticks. Ten of the 38 serpin genes were expressed from six to 24 hrs of feeding while six and fives genes each are predominantly or exclusively expressed in either MG and SG respectively. Conclusion Given the diversity among tick species, sizes of tick serpin families are likely to be variable. However this study provides insight on the potential sizes of serpin protein families in ticks. Ticks must overcome inflammation, complement activation and blood coagulation to complete feeding. Since these pathways are regulated by serpins that have basic residues at their P1 sites, we speculate that I. scapularis may utilize some of the serpins reported in this study to manipulate host defense. We have discussed our data in the context of

  1. Comparison of MAPK specificity across the ETS transcription factor family identifies a high-affinity ERK interaction required for ERG function in prostate cells.

    Science.gov (United States)

    Selvaraj, Nagarathinam; Kedage, Vivekananda; Hollenhorst, Peter C

    2015-02-19

    The RAS/MAPK signaling pathway can regulate gene expression by phosphorylating and altering the function of some, but not all, ETS transcription factors. ETS family transcription factors bind similar DNA sequences and can compete for genomic binding sites. However, MAPK regulation varies across the ETS family. Therefore, changing the ETS factor bound to a cis-regulatory element can alter MAPK regulation of gene expression. To understand RAS/MAPK regulated gene expression programs, comprehensive knowledge of the ETS family members that are MAPK targets and relative MAPK targeting efficiency across the family is needed. An in vitro kinase assay was used to rank-order 27 human ETS family transcription factors based on phosphorylation by ERK2, JNK1, and p38α. Many novel MAPK targets and specificities were identified within the ETS family, including the identification of the prostate cancer oncoprotein ERG as a specific target of ERK2. ERK2 phosphorylation of ERG S215 required a DEF docking domain and was necessary for ERG to activate transcription of cell migration genes and promote prostate cell migration. The ability of ERK2 to bind ERG with higher affinity than ETS1 provided a potential molecular explanation for why ERG overexpression drives migration of prostate cells with low levels of RAS/ERK signaling, while ETS1 has a similar function only when RAS/ERK signaling is high. The rank ordering of ETS transcription factors as MAPK targets provides an important resource for understanding ETS proteins as mediators of MAPK signaling. This is emphasized by the difference in rank order of ERG and ETS1, which allows these factors to have distinct roles based on the level of RAS/ERK signaling present in the cell.

  2. Stimulation of BK virus DNA replication by NFI family transcription factors.

    Science.gov (United States)

    Liang, Bo; Tikhanovich, Irina; Nasheuer, Heinz Peter; Folk, William R

    2012-03-01

    BK polyomavirus (BKV) establishes persistent, low-level, and asymptomatic infections in most humans and causes polyomavirus-associated nephropathy (PVAN) and other pathologies in some individuals. The activation of BKV replication following kidney transplantation, leading to viruria, viremia, and, ultimately, PVAN, is associated with immune suppression as well as inflammation and stress from ischemia-reperfusion injury of the allograft, but the stimuli and molecular mechanisms leading to these pathologies are not well defined. The replication of BKV DNA in cell cultures is regulated by the viral noncoding control region (NCCR) comprising the core origin and flanking sequences, to which BKV T antigen (Tag), cellular proteins, and small regulatory RNAs bind. Six nuclear factor I (NFI) binding sites occur in sequences flanking the late side of the core origin (the enhancer) of the archetype virus, and their mutation, either individually or in toto, reduces BKV DNA replication when placed in competition with templates containing intact BKV NCCRs. NFI family members interacted with the helicase domain of BKV Tag in pulldown assays, suggesting that NFI helps recruit Tag to the viral core origin and may modulate its function. However, Tag may not be the sole target of the replication-modulatory activities of NFI: the NFIC/CTF1 isotype stimulates BKV template replication in vitro at low concentrations of DNA polymerase-α primase (Pol-primase), and the p58 subunit of Pol-primase associates with NFIC/CTF1, suggesting that NFI also recruits Pol-primase to the NCCR. These results suggest that NFI proteins (and the signaling pathways that target them) activate BKV replication and contribute to the consequent pathologies caused by acute infection.

  3. C68 from the Sulfolobus islandicus plasmid-virus pSSVx is a novel member of the AbrB-like transcription factor family

    DEFF Research Database (Denmark)

    Contursi, Patrizia; D'Ambrosio, Katia; Pirone, Luciano

    2011-01-01

    that are located upstream of its own promoter. The three-dimensional structure, solved by a single-wavelength anomalous diffraction experiment on a selenomethionine derivative, shows that the protein assumes a swapped-hairpin fold, which is a distinctive fold associated with a family of prokaryotic transcription...

  4. Design and Assessment of a Real Time Reverse Transcription-PCR Method to Genotype Single-Stranded RNA Male-Specific Coliphages (Family Leviviridae).

    Science.gov (United States)

    A real-time, reverse transcription-PCR (RT-qPCR) assay was developed to differentiate the four genogroups of male-specific ssRNA coliphages (FRNA) (family Leviviridae). As FRNA display a trend of source-specificity (human sewage or animal waste) at the genogroup level, this assa...

  5. GALNT3, a gene associated with hyperphosphatemic familial tumoral calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity

    OpenAIRE

    2008-01-01

    GALNT3, a gene associated with Hyperphosphatemic Familial Tumoral Calcinosis, is transcriptionally regulated by extracellular phosphate and modulates matrix metalloproteinase activity correspondence: Corresponding author. Laboratory of Molecular Dermatology Department of Dermatology Rambam Medical Center POB 9602, Haifa 31096, Israel. Tel.: +972 4 8541919; fax: +972 4 8542951. (Sprecher, Eli) (Sprecher, Eli) Labo...

  6. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription

    DEFF Research Database (Denmark)

    Cartwright, P; Müller, H; Wagener, C;

    1998-01-01

    promoter (TTTCGCGC). In contrast to the other members of the E2F family, ectopic expression of E2F-6 inhibits transcription from promoters possessing E2F recognition sites rather than activating transcription. In addition, overexpression of E2F-6 suppresses the transactivational effects of coexpression......The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes......, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology...

  7. Common and distinct DNA-binding and regulatory activities of the BEN-solo transcription factor family.

    Science.gov (United States)

    Dai, Qi; Ren, Aiming; Westholm, Jakub O; Duan, Hong; Patel, Dinshaw J; Lai, Eric C

    2015-01-01

    properties of this new family of transcription factors.

  8. Knock-down of transcript abundance of a family of Kunitz proteinase inhibitor genes in white clover (Trifolium repens) reveals a redundancy and diversity of gene function.

    Science.gov (United States)

    Islam, Afsana; Leung, Susanna; Burgess, Elisabeth P J; Laing, William A; Richardson, Kim A; Hofmann, Rainer W; Dijkwel, Paul P; McManus, Michael T

    2015-12-01

    The transcriptional regulation of four phylogenetically distinct members of a family of Kunitz proteinase inhibitor (KPI) genes isolated from white clover (Trifolium repens; designated Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5) has been investigated to determine their wider functional role. The four genes displayed differential transcription during seed germination, and in different tissues of the mature plant, and transcription was also ontogenetically regulated. Heterologous over-expression of Tr-KPI1, Tr-KPI2, Tr-KPI4 and Tr-KPI5 in Nicotiana tabacum retarded larval growth of the herbivore Spodoptera litura, and an increase in the transcription of the pathogenesis-related genes PR1 and PR4 was observed in the Tr-KPI1 and Tr-KPI4 over-expressing lines. RNA interference (RNAi) knock-down lines in white clover displayed significantly altered vegetative growth phenotypes with inhibition of shoot growth and a stimulation of root growth, while knock-down of Tr-KPI1, Tr-KPI2 and Tr-KPI5 transcript abundance also retarded larval growth of S. litura. Examination of these RNAi lines revealed constitutive stress-associated phenotypes as well as altered transcription of cellular signalling genes. These results reveal a functional redundancy across members of the KPI gene family. Further, the regulation of transcription of at least one member of the family, Tr-KPI2, may occupy a central role in the maintenance of a cellular homeostasis.

  9. Aquaporin family genes exhibit developmentally-regulated and host-dependent transcription patterns in the sea louse Caligus rogercresseyi.

    Science.gov (United States)

    Farlora, Rodolfo; Valenzuela-Muñoz, Valentina; Chávez-Mardones, Jacqueline; Gallardo-Escárate, Cristian

    2016-07-01

    Aquaporins are small integral membrane proteins that function as pore channels for the transport of water and other small solutes across the cell membrane. Considering the important roles of these proteins in several biological processes, including host-parasite interactions, there has been increased research on aquaporin proteins recently. The present study expands on the knowledge of aquaporin family genes in parasitic copepods, examining diversity and expression during the ontogeny of the sea louse Caligus rogercresseyi. Furthermore, aquaporin expression was evaluated during the early infestation of Atlantic (Salmo salar) and Coho salmon (Oncorhynchus kisutch). Deep transcriptome sequencing data revealed eight full length and two partial open reading frames belonging to the aquaporin protein family. Clustering analyses with identified Caligidae sequences revealed three major clades of aquaglyceroporins (Cr-Glp), classical aquaporin channels (Cr-Bib and Cr-PripL), and unorthodox aquaporins (Cr-Aqp12-like). In silico analysis revealed differential expression of aquaporin genes between developmental stages and between sexes. Male-biased expression of Cr-Glp1_v1 and female-biased expression of Cr-Bib were further confirmed in adults by RT-qPCR. Additionally, gene expressions were measured for seven aquaporins during the early infestation stage. The majority of aquaporin genes showed significant differential transcription expressions between sea lice parasitizing different hosts, with Atlantic salmon sea lice exhibiting overall reduced expression as compared to Coho salmon. The observed differences in the regulation of aquaporin genes may reveal osmoregulatory adaptations associated with nutrient ingestion and metabolite waste export, exposing complex host-parasite relationships in C. rogercresseyi.

  10. Achilles, a New Family of Transcriptionally Active Retrotransposons from the Olive Fruit Fly, with Y Chromosome Preferential Distribution.

    Directory of Open Access Journals (Sweden)

    Konstantina T Tsoumani

    Full Text Available Sex chromosomes have many unusual features relative to autosomes. The in depth exploration of their structure will improve our understanding of their origin and divergence (degeneration as well as the evolution of genetic sex determination pathways which, most often are attributed to them. In Tephritids, the structure of Y chromosome, where the male-determining factor M is localized, is largely unexplored and limited data concerning its sequence content and evolution are available. In order to get insight into the structure and organization of the Y chromosome of the major olive insect pest, the olive fly Bactrocera oleae, we characterized sequences from a Pulse Field Gel Electrophoresis (PFGE-isolated Y chromosome. Here, we report the discovery of the first olive fly LTR retrotransposon with increased presence on the Y chromosome. The element belongs to the BEL-Pao superfamily, however, its sequence comparison with the other members of the superfamily suggests that it constitutes a new family that we termed Achilles. Its ~7.5 kb sequence consists of the 5'LTR, the 5'non-coding sequence and the open reading frame (ORF, which encodes the polyprotein Gag-Pol. In situ hybridization to the B. oleae polytene chromosomes showed that Achilles is distributed in discrete bands dispersed on all five autosomes, in all centromeric regions and in the granular heterochromatic network corresponding to the mitotic sex chromosomes. The between sexes comparison revealed a variation in Achilles copy number, with male flies possessing 5-10 copies more than female (CI range: 18-38 and 12-33 copies respectively per genome. The examination of its transcriptional activity demonstrated the presence of at least one intact active copy in the genome, showing a differential level of expression between sexes as well as during embryonic development. The higher expression was detected in male germline tissues (testes. Moreover, the presence of Achilles-like elements in

  11. Members of the barley NAC transcription factor gene family show differential co-regulation with senescence-associated genes during senescence of flag leaves

    DEFF Research Database (Denmark)

    Christiansen, Michael W; Gregersen, Per L.

    2014-01-01

    The senescence process of plants is important for the completion of their life cycle, particularly for crop plants, it is essential for efficient nutrient remobilization during seed filling. It is a highly regulated process, and in order to address the regulatory aspect, the role of genes...... in the NAC transcription factor family during senescence of barley flag leaves was studied. Several members of the NAC transcription factor gene family were up-regulated during senescence in a microarray experiment, together with a large range of senescence-associated genes, reflecting the coordinated...... activation of degradation processes in senescing barley leaf tissues. This picture was confirmed in a detailed quantitative reverse transcription–PCR (qRT–PCR) experiment, which also showed distinct gene expression patterns for different members of the NAC gene family, suggesting a group of ~15 out of the 47...

  12. Heterogeneous dynamics in DNA site discrimination by the structurally homologous DNA-binding domains of ETS-family transcription factors.

    Science.gov (United States)

    He, Gaofei; Tolic, Ana; Bashkin, James K; Poon, Gregory M K

    2015-04-30

    The ETS family of transcription factors exemplifies current uncertainty in how eukaryotic genetic regulators with overlapping DNA sequence preferences achieve target site specificity. PU.1 and Ets-1 represent archetypes for studying site discrimination by ETS proteins because their DNA-binding domains are the most divergent in sequence, yet they share remarkably superimposable DNA-bound structures. To gain insight into the contrasting thermodynamics and kinetics of DNA recognition by these two proteins, we investigated the structure and dynamics of site discrimination by their DNA-binding domains. Electrophoretic mobilities of complexes formed by the two homologs with circularly permuted binding sites showed significant dynamic differences only for DNA complexes of PU.1. Free solution measurements by dynamic light scattering showed PU.1 to be more dynamic than Ets-1; moreover, dynamic changes are strongly coupled to site discrimination by PU.1, but not Ets-1. Interrogation of the protein/DNA interface by DNA footprinting showed similar accessibility to dimethyl sulfate for PU.1/DNA and Ets-1/DNA complexes, indicating that the dynamics of PU.1/DNA complexes reside primarily outside that interface. An information-based analysis of the two homologs' binding motifs suggests a role for dynamic coupling in PU.1's ability to enforce a more stringent sequence preference than Ets-1 and its proximal sequence homologs. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains.

    Science.gov (United States)

    Stephens, Dominique C; Poon, Gregory M K

    2016-10-14

    Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi-methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Plant transcription factors from the homeodomain-leucine zipper family I. Role in development and stress responses.

    Science.gov (United States)

    Perotti, María Florencia; Ribone, Pamela Anahí; Chan, Raquel Lía

    2017-05-01

    In front of stressful conditions plants display adaptation mechanisms leading to changes in their morphology, physiology, development and molecular composition. Transcription factors (TFs) play crucial roles in these complex adaptation processes. This work is focused in the homeodomain-leucine zipper I (HD-Zip I) family of TFs, unique to plants. First discovered in 1991, they were identified and isolated from monocotyledonous and dicotyledonous plants showing high structural similarity and diversified functions. These TFs have, besides the homeodomain and leucine zipper, conserved motifs in their carboxy-termini allowing the interaction with the basal machinery and with other regulatory proteins. The model dicotyledonous plant Arabidopsis thaliana has 17 HD-Zip I members; most of them regulated by external stimuli and hormones. These TFs are involved in key developmental processes like root and stem elongation, rosette leaves morphology determination, inflorescence stem branching, flowering and pollen hydration. Moreover, they are key players in responses to environmental stresses and illumination conditions. Several HD-Zip I encoding genes from different species were protected in patents because their overexpression or mutation generates improved agronomical phenotypes. Here we discuss many aspects about these TFs including structural features, biological functions and their utilization as biotechnological tools to improve crops. © 2017 IUBMB Life, 69(5):280-289, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  15. Genome-wide identification, classification, and analysis of heat shock transcription factor family in Chinese cabbage (Brassica rapa pekinensis).

    Science.gov (United States)

    Huang, X Y; Tao, P; Li, B Y; Wang, W H; Yue, Z C; Lei, J L; Zhong, X M

    2015-03-27

    Chinese cabbage (Brassica rapa ssp. pekinensis) is one of the most important vegetable crops grown worldwide, and various methods exist for selection, propagation, and cultivation. The entire Chinese cabbage genome has been sequenced, and the heat shock transcription factor family (Hsfs) has been found to play a central role in plant growth and development and in the response to biotic and abiotic stress conditions, particularly in acquired thermotolerance. We analyzed heat tolerance mechanisms in Chinese cabbage. In this study, 30 Hsfs were identified from the Chinese cabbage genome database. The classification, phylogenetic reconstruction, chromosome distribution, conserved motifs, expression analysis, and interaction networks of the Hsfs were predicted and analyzed. Thirty BrHsfs were classified into 3 major classes (class A, B, and C) according to their structural characteristics and phylogenetic comparisons, and class A was further subdivided into 8 subclasses. Distribution mapping results showed that Hsf genes were located on 10 Chinese cabbage chromosomes. The expression profile indicated that Hsfs play differential roles in 5 organs in Chinese cabbage, and likely participate in the development of underground parts and regulation of reproductive growth. An orthologous gene interaction network was constructed, and included MBF1C, ROF1, TBP2, CDC2, and HSP70 5 genes, which are closely related to heat stress. Our results contribute to the understanding of the complexity of Hsfs in Chinese cabbage and provide a basis for further functional gene research.

  16. Expression of the meningococcal adhesin NadA is controlled by a transcriptional regulator of the MarR family.

    Science.gov (United States)

    Schielke, Stephanie; Huebner, Claudia; Spatz, Carolin; Nägele, Virginie; Ackermann, Nikolaus; Frosch, Matthias; Kurzai, Oliver; Schubert-Unkmeir, Alexandra

    2009-05-01

    Two closely related pathogenic species have evolved in the genus Neisseria: N. meningitidis and N. gonorrhoeae, which occupy different host niches and cause different clinical entities. In contrast to the pathogen N. gonorrhoeae, N. meningitidis is a commensal and only rarely becomes invasive. Little is known about the genetic background of the entirely different lifestyles in these closely related species. Meningococcal NMB1843 encodes a transcriptional regulator of the MarR family. The gonococcal homologue FarR regulates expression of farAB, mediating fatty acid resistance. We show that NmFarR also directly interacts with NmfarAB. Yet, by contrast to N. gonorrhoeae, no significant sensitivity to fatty acids was observed in a DeltafarR mutant due to intrinsic resistance of meningococci. Further analyses identified an NmFarR-repressed protein absent from N. gonorrhoeae. This protein is the meningococcus-specific adhesin and vaccine component NadA that has most likely been acquired by horizontal gene transfer. NmFarR binds to a 16 base pair palindromic repeat within the nadA promoter. De-repression of nadA resulted in significantly higher association of a DeltafarR strain with epithelial cells. Hence NmFarR has gained control over a meningococcus-specific gene involved in host colonization and thus contributed to divergent niche adaptation in pathogenic Neisseriae.

  17. CREB-regulated transcription co-activator family stimulates promoter II-driven aromatase expression in preadipocytes.

    Science.gov (United States)

    Samarajeewa, Nirukshi U; Docanto, Maria M; Simpson, Evan R; Brown, Kristy A

    2013-08-01

    The dramatically increased prevalence of breast cancer after menopause is of great concern and is correlated with elevated local levels of estrogens. This is mainly due to an increase in aromatase expression driven by its proximal promoter II (PII). We have previously demonstrated that the CREB co-activator CRTC2 binds directly to PII and stimulates its activity via mechanisms involving LKB1-AMPK in response to prostaglandin E(2) (PGE(2)). There are three members of the CRTC family (CRTC1-3) and this study aimed to characterize the role of other CRTCs in the activation of aromatase PII. The expression and subcellular localization of CRTCs were examined in preadipocytes using qPCR and immunofluorescence. Under basal conditions, CRTC1 expression was the lowest, whereas CRTC3 transcripts were present at higher levels. Basally, CRTC2 and CRTC3 were mainly cytoplasmic and PGE(2) caused their nuclear translocation. Reporter assays and chromatin immunoprecipitation (ChIP) were performed to assess the effect of CRTCs on PII activity and binding. Basal PII activity was significantly increased with all CRTCs. Forskolin (FSK)/phorbol 12-myristate 13-acetate (PMA), to mimic PGE(2), resulted in a further significant increase in PII activity with all CRTCs, with CRTC2 and CRTC3 having greater effects. This was consistent with ChIP data showing an increased binding of CRTCs to PII with FSK/PMA. Moreover, gene silencing of CRTC2 and CRTC3 significantly reduced the FSK/PMA-mediated stimulation of aromatase activity. Interestingly, CRTCs acted cooperatively with CREB1 to increase PII activity, and both CREs were found to be essential for the maximal induction of PII activity by CRTCs. Phosphorylation of CRTC2 at its AMPK target site, Ser 171, dictated its subcellular localization, and the activation of aromatase PII in preadipocytes. In conclusion, this study demonstrates that aromatase regulation in primary human breast preadipocytes involves more than one CRTC.

  18. Characterization of three Arabidopsis AP2/EREBP family transcription factors involved in ABA sensitivity,freeze and salt tolerance

    Institute of Scientific and Technical Information of China (English)

    MEI WenQian; LEI Juan; Xu Yu; WEI Gang; ZHU YuXian

    2007-01-01

    AP2/EREBP transcription factors (TFs) play very important roles in plant development,hormonal regulation and stress response. Upon genome-wide cDNA cloning,phylogenetic and expression pattern analyses of this plant specific TF family,we found that three of the members including At1g71450,At1g50680 and At5g13910,were likely involved in responses to ABA,cold and salt. Complementary DNAs containing putative full-length ORFs of these three TFs were obtained and fused individually to the GAL4 DNA-binding domains. All the 3 genes functioned effectively as trans-activators using yeast one-hybrid assays. RT-PCR experiments showed that the At1g71450 gene was induced by ABA and low temperature; the At1g50680 gene was responsive to quite a few stress conditions,but especially to freezing temperature; and the At5g13910 gene was induced by high salt treatment,drought and ethylene. By searching the ABRC T-DNA insertion mutant stocks,we obtained knockout lines for these TFs. Homozygous ko1 (At1g71450) plants showed a hypersensitive response to ABA during seed germination and also in stomata movement. Homozygous ko2 (At1g50680) plants showed a significant reduction in plant freezing tolerance compared to the wild type after chilling treatment. Homozygous ko3 (At5g13910) were less tolerant to high salinity than wild type plants. Our data suggest that At1g71450 is a negative regulator in ABA signaling,while At1g50680 and At5g13910 are positive regulators in cold and salt stress responses,respectively.

  19. Transposon mutagenesis reveals cooperation of ETS family transcription factors with signaling pathways in erythro-megakaryocytic leukemia.

    Science.gov (United States)

    Tang, Jian Zhong; Carmichael, Catherine L; Shi, Wei; Metcalf, Donald; Ng, Ashley P; Hyland, Craig D; Jenkins, Nancy A; Copeland, Neal G; Howell, Viive M; Zhao, Zhizhuang Joe; Smyth, Gordon K; Kile, Benjamin T; Alexander, Warren S

    2013-04-09

    To define genetic lesions driving leukemia, we targeted cre-dependent Sleeping Beauty (SB) transposon mutagenesis to the blood-forming system using a hematopoietic-selective vav 1 oncogene (vav1) promoter. Leukemias of diverse lineages ensued, most commonly lymphoid leukemia and erythroleukemia. The inclusion of a transgenic allele of Janus kinase 2 (JAK2)V617F resulted in acceleration of transposon-driven disease and strong selection for erythroleukemic pathology with transformation of bipotential erythro-megakaryocytic cells. The genes encoding the E-twenty-six (ETS) transcription factors Ets related gene (Erg) and Ets1 were the most common sites for transposon insertion in SB-induced JAK2V617F-positive erythroleukemias, present in 87.5% and 65%, respectively, of independent leukemias examined. The role of activated Erg was validated by reproducing erythroleukemic pathology in mice transplanted with fetal liver cells expressing translocated in liposarcoma (TLS)-ERG, an activated form of ERG found in human leukemia. Via application of SB mutagenesis to TLS-ERG-induced erythroid transformation, we identified multiple loci as likely collaborators with activation of Erg. Jak2 was identified as a common transposon insertion site in TLS-ERG-induced disease, strongly validating the cooperation between JAK2V617F and transposon insertion at the Erg locus in the JAK2V617F-positive leukemias. Moreover, loci expressing other regulators of signal transduction pathways were conspicuous among the common transposon insertion sites in TLS-ERG-driven leukemia, suggesting that a key mechanism in erythroleukemia may be the collaboration of lesions disturbing erythroid maturation, most notably in genes of the ETS family, with mutations that reduce dependence on exogenous signals.

  20. Identification and characterization of NF-Y transcription factor families in the monocot model plant Brachypodium distachyon.

    Directory of Open Access Journals (Sweden)

    Shuanghe Cao

    Full Text Available BACKGROUND: Nuclear Factor Y (NF-Y is a heterotrimeric transcription factor composed of NF-YA, NF-YB and NF-YC proteins. Using the dicot plant model system Arabidopsis thaliana (Arabidopsis, NF-Y were previously shown to control a variety of agronomically important traits, including drought tolerance, flowering time, and seed development. The aim of the current research was to identify and characterize NF-Y families in the emerging monocot model plant Brachypodium distachyon (Brachypodium with the long term goal of assisting in the translation of known dicot NF-Y functions to the grasses. METHODOLOGY/PRINCIPAL FINDINGS: We identified, annotated, and further characterized 7 NF-YA, 17 NF-YB, and 12 NF-YC proteins in Brachypodium (BdNF-Y. By examining phylogenetic relationships, orthology predictions, and tissue-specific expression patterns for all 36 BdNF-Y, we proposed numerous examples of likely functional conservation between dicots and monocots. To test one of these orthology predictions, we demonstrated that a BdNF-YB with predicted orthology to Arabidopsis floral-promoting NF-Y proteins can rescue a late flowering Arabidopsis mutant. CONCLUSIONS/SIGNIFICANCE: The Brachypodium genome encodes a similar complement of NF-Y to other sequenced angiosperms. Information regarding NF-Y phylogenetic relationships, predicted orthologies, and expression patterns can facilitate their study in the grasses. The current data serves as an entry point for translating many NF-Y functions from dicots to the genetically tractable monocot model system Brachypodium. In turn, studies of NF-Y function in Brachypodium promise to be more readily translatable to the agriculturally important grasses.

  1. Diverse Transcriptional Programs Associated with Environmental Stress and Hormones in the Arabidopsis Receptor-Like Kinase Gene Family

    Institute of Scientific and Technical Information of China (English)

    Lee Chae; Sylvia Sudat; Sandrine Dudoit; Tong Zhu; Sheng Luan

    2009-01-01

    The genome of Arabidopsis thaliana encodes more than 600 receptor-like kinase (RLK) genes, by far the dominant class of receptors found in land plants. Although similar to the mammalian receptor tyrosine kinases, plant RLKs are serine/threonine kinases that represent a novel signaling innovation unique to plants and, consequently, an excellent opportunity to understand how extracellular signaling evolved and functions in plants as opposed to animals. RLKs are predicted to be major components of the signaling pathways that allow plants to respond to environmental and developmental conditions. However, breakthroughs in identifying these processes have been limited to only a handful of individual RLKs. Here, we used a Syngenta custom Arabidopsis GeneChip array to compile a detailed profile of the transcriptional activity of 604 receptor-like kinase genes after exposure to a cross-section of known signaling factors in plants,including abiotic stresses, biotic stresses, and hormones. In the 68 experiments comprising the study, we found that 582 of the 604 RLK genes displayed a two-fold or greater change in expression to at least one of 12 types of treatments, thereby providing a large body of experimental evidence for targeted functional screens of individual RLK genes. We investigated whether particular subfamilies of RLK genes are responsive to specific types of signals and found that each subfamily displayed broad ranges of expression, as opposed to being targeted towards particular signal classes. Finally, by analyzing the divergence of sequence and gene expression among the RLK subfamilies, we present evidence as to the functional basis for the expansion of the RLKs and how this expansion may have affected conservation and divergences in their function. Taken as a whole, our study represents a preliminary, working model of processes and interactions in which the members of the RLK gene family may be involved, where such information has remained elusive for so many

  2. Forkhead transcription factor FOXF1 is a novel target gene of the p53 family and regulates cancer cell migration and invasiveness.

    Science.gov (United States)

    Tamura, M; Sasaki, Y; Koyama, R; Takeda, K; Idogawa, M; Tokino, T

    2014-10-01

    p53 is an established tumor suppressor that can activate the transcription of multiple target genes. Recent evidence suggests that p53 may contribute to the regulation of cell invasion and migration. In this study, we show that the forkhead box transcription factor FOXF1 is a novel target of the p53 family because FOXF1 is upregulated by p53, TAp73 and TAp63. We show that FOXF1 is induced upon DNA damage in a p53-dependent manner. Furthermore, we identified a response element located within the FOXF1 gene that is responsive to wild-type p53, TAp73β and TAp63γ. The ectopic expression of FOXF1 inhibited cancer cell invasion and migration, whereas the inactivation of FOXF1 stimulated cell invasion and migration. We also show that FOXF1 regulates the transcriptional activity of E-cadherin (CDH1) by acting on its FOXF1 consensus binding site located upstream of the E-cadherin gene. Collectively, our results show that FOXF1 is a p53 family target gene, and our data suggest that FOXF1 and p53 form a portion of a regulatory transcriptional network that appears to have an important role in cancer cell invasion and migration.

  3. Genome-wide identification, classification and functional analyses of the bHLH transcription factor family in the pig, Sus scrofa.

    Science.gov (United States)

    Liu, Wuyi

    2015-08-01

    The basic helix-loop-helix (bHLH) transcription factors are one of the largest families of gene regulatory proteins and play crucial roles in genetic, developmental and physiological processes in eukaryotes. Here, we conducted a survey of the Sus scrofa genome and identified 109 putative bHLH transcription factor members belonging to super-groups A, B, C, D, E, and F, respectively, while four members were orphan genes. We identified 6 most significantly enriched KEGG pathways and 116 most significant GO annotation categories. Further comprehensive surveys in human genome and other 12 medical databases identified 72 significantly enriched biological pathways with these 113 pig bHLH transcription factors. From the functional protein association network analysis 93 hub proteins were identified and 55 hub proteins created a tight network or a functional module within their protein families. Especially, there were 20 hub proteins found highly connected in the functional interaction network. The present study deepens our understanding and provided insights into the evolution and functional aspects of animal bHLH proteins and should serve as a solid foundation for further for analyses of specific bHLH transcription factors in the pig and other mammals.

  4. Engineering of the TetR family transcriptional regulator SAV151 and its target genes increases avermectin production in Streptomyces avermitilis.

    Science.gov (United States)

    He, Fei; Liu, Wenshuai; Sun, Di; Luo, Shuai; Chen, Zhi; Wen, Ying; Li, Jilun

    2014-01-01

    Avermectins produced by Streptomyces avermitilis are used commercially for broad-spectrum parasite control in medical, veterinary, and agricultural fields. Our previous comparative transcriptome analysis of wild-type strain ATCC31267 vs. avermectin-overproducing strain 76-02-e revealed that the gene SAV151, which encodes a TetR family transcriptional regulator, was downregulated in 76-02-e. In the present study, we investigated the role of SAV151 in avermectin production. Deletion of SAV151 increased avermectin yield ~1-fold in ATCC31267, and this phenotype was complemented by a single copy of SAV151. Overexpression of SAV151 in ATCC31267 reduced avermectin yield by ~70%. RT-PCR analysis showed that the promoting effect of SAV151 deletion on avermectin production was not due to alteration of ave genes at the transcriptional level. SAV151 negatively regulated the transcription of itself and of the adjacent transcriptional unit SAV152-SAV153-SAV154. In chromatin immunoprecipitation and gel shift assays, purified His6-tagged SAV151 protein bound to the bidirectional SAV151-SAV152 promoter region. SAV151 bound to two palindromic sequences in this region and thereby repressed transcription from both directions. Two of the SAV151 target genes, SAV152 (which encodes a putative dehydrogenase) and SAV154 (which encodes a putative hydrolase), had promoting effects on avermectin production. Our findings provide the basis for a strategy to increase avermectin production by controlling SAV151 and its target genes.

  5. Endo-(1,4-β-Glucanase gene families in the grasses: temporal and spatial Co-transcription of orthologous genes1

    Directory of Open Access Journals (Sweden)

    Buchanan Margaret

    2012-12-01

    Full Text Available Abstract Background Endo-(1,4-β-glucanase (cellulase glycosyl hydrolase GH9 enzymes have been implicated in several aspects of cell wall metabolism in higher plants, including cellulose biosynthesis and degradation, modification of other wall polysaccharides that contain contiguous (1,4-β-glucosyl residues, and wall loosening during cell elongation. Results The endo-(1,4-β-glucanase gene families from barley (Hordeum vulgare, maize (Zea mays, sorghum (Sorghum bicolor, rice (Oryza sativa and Brachypodium (Brachypodium distachyon range in size from 23 to 29 members. Phylogenetic analyses show variations in clade structure between the grasses and Arabidopsis, and indicate differential gene loss and gain during evolution. Map positions and comparative studies of gene structures allow orthologous genes in the five species to be identified and synteny between the grasses is found to be high. It is also possible to differentiate between homoeologues resulting from ancient polyploidizations of the maize genome. Transcript analyses using microarray, massively parallel signature sequencing and quantitative PCR data for barley, rice and maize indicate that certain members of the endo-(1,4-β-glucanase gene family are transcribed across a wide range of tissues, while others are specifically transcribed in particular tissues. There are strong correlations between transcript levels of several members of the endo-(1,4-β-glucanase family and the data suggest that evolutionary conservation of transcription exists between orthologues across the grass family. There are also strong correlations between certain members of the endo-(1,4-β-glucanase family and other genes known to be involved in cell wall loosening and cell expansion, such as expansins and xyloglucan endotransglycosylases. Conclusions The identification of these groups of genes will now allow us to test hypotheses regarding their functions and joint participation in wall synthesis, re

  6. Lack of germline A339V mutation in thyroid transcription factor-1 (TITF-1/NKX2.1 gene in familial papillary thyroid cancer

    Directory of Open Access Journals (Sweden)

    Cantara Silvia

    2010-08-01

    Full Text Available Abstract Thyroid cancer may have a familial predisposition but a specific germline alteration responsible for the disease has not been discovered yet. We have shown that familial papillary thyroid cancer (FPTC patients have an imbalance in telomere-telomerase complex with short telomeres and increased telomerase activity. A germline mutation (A339V in thyroid transcription factor-1 has been described in patients with multinodular goiter and papillary thyroid cancer. In this report, the presence of the A339V mutation and the telomere length has been studied in FPTC patients and unaffected family members. All samples analyzed displayed a pattern typical of the homozygous wild type revealing the absence of the A339V mutation. Shortening of telomeres was confirmed in all patients. We concluded that the A339V mutation in thyroid transcription factor-1 (TITF-1/NKX2.1 is not correlated with the familial form of PTC, even when the tumor was in the context of multinodular goiter.

  7. HosA, a MarR Family Transcriptional Regulator, Represses Nonoxidative Hydroxyarylic Acid Decarboxylase Operon and Is Modulated by 4-Hydroxybenzoic Acid.

    Science.gov (United States)

    Roy, Ajit; Ranjan, Akash

    2016-02-23

    Members of the Multiple antibiotic resistance Regulator (MarR) family of DNA binding proteins regulate transcription of a wide array of genes required for virulence and pathogenicity of bacteria. The present study reports the molecular characterization of HosA (Homologue of SlyA), a MarR protein, with respect to its target gene, DNA recognition motif, and nature of its ligand. Through a comparative genomics approach, we demonstrate that hosA is in synteny with nonoxidative hydroxyarylic acid decarboxylase (HAD) operon and is present exclusively within the mutS-rpoS polymorphic region in nine different genera of Enterobacteriaceae family. Using molecular biology and biochemical approach, we demonstrate that HosA binds to a palindromic sequence downstream to the transcription start site of divergently transcribed nonoxidative HAD operon and represses its expression. Furthermore, in silico analysis showed that the recognition motif for HosA is highly conserved in the upstream region of divergently transcribed operon in different genera of Enterobacteriaceae family. A systematic chemical search for the physiological ligand revealed that 4-hydroxybenzoic acid (4-HBA) interacts with HosA and derepresses HosA mediated repression of the nonoxidative HAD operon. Based on our study, we propose a model for molecular mechanism underlying the regulation of nonoxidative HAD operon by HosA in Enterobacteriaceae family.

  8. Expression, Functional Characterization and X-ray Analysis of HosA, A Member of MarR Family of Transcription Regulator from Uropathogenic Escherichia coli.

    Science.gov (United States)

    Roy, Ajit; Reddi, Ravikumar; Sawhney, Bhavik; Ghosh, Debasish Kumar; Addlagatta, Anthony; Ranjan, Akash

    2016-08-01

    Regulators belonging to multiple antibiotic resistance regulator (MarR) family are widespread in prokaryotes and are involved in regulation of genes that are responsible for virulence and pathogenicity in most of the clinically important pathogens. Here we report the transcriptional, biophysical, and X-ray analyses of homologue of SlyA (HosA), a member of MarR family that is predominantly present in the pathogenic strains of Enterobacteriaceae family. The initiation of hosA transcription was observed to occur at two independent start sites and subsequent binding study has revealed that the purified HosA interacts with its upstream region suggesting a probable autoregulation. The secondary structure analysis through circular dichroism spectroscopy demonstrated that HosA is predominantly composed of the alpha helix with higher thermal stability. To further understand the three-dimensional structure, HosA was crystallized and the crystals were diffracted to maximum of 2.9 Ǻ on exposure to X-rays. Analysis of the X-ray crystallographic data suggested a primitive space group (P 6 ? 2 2), with unit cell parameters a = b = 64.19 Å and c = 244.25 Å. The solvent content and Matthews coefficient were 41 % and 2.11 Å(3) Da(-1), respectively, which indicated the existence of two molecules of HosA in the asymmetric unit of crystal.

  9. Structure of an MmyB-like regulator from C. aurantiacus, member of a new transcription factor family linked to antibiotic metabolism in actinomycetes.

    Directory of Open Access Journals (Sweden)

    Qingping Xu

    Full Text Available Actinomycetes are important bacterial sources of antibiotics and other secondary metabolites. Many antibiotic gene clusters are controlled by pathway-specific activators that act in response to growth conditions. Here we present the crystal structure of an MmyB-like transcription regulator MltR (PDB code 3pxp (Caur_2278 from Chloroflexus aurantiacus, in complex with a fatty acid (myristic acid. MltR is a distant homolog of the methylenomycin activator MmyB and consists of an Xre-type N-terminal DNA-binding domain and a C-terminal ligand-binding module that is related to the Per-Arnt-Sim (PAS domain. This structure has enabled identification of a new family of bacterial transcription factors that are distributed predominantly in actinomycetes. Bioinformatics analysis of MltR and other characterized family members suggest that they are likely associated with antibiotic and fatty acid metabolism in actinomycetes. Streptomyces coelicolor SCO4944 is a candidate as an ancestral member of the family. Its ortholog in S. griseus, SGR_6891, is induced by A-factor, a γ-butyrolactone that controls antibiotic production and development, and is adjacent to the A-factor synthase gen, afsA. The location of mltR/mmyB homologs, in particular those adjacent to less well-studied antibiotic-related genes, makes them interesting genetic markers for identifying new antibiotic genes. A model for signal-triggered DNA-binding by MltR is proposed.

  10. Identification and characterization of novel parathyroid-specific transcription factor Glial Cells Missing Homolog B (GCMB) mutations in eight families with autosomal recessive hypoparathyroidism.

    Science.gov (United States)

    Bowl, Michael R; Mirczuk, Samantha M; Grigorieva, Irina V; Piret, Sian E; Cranston, Treena; Southam, Lorraine; Allgrove, Jeremy; Bahl, Shailini; Brain, Caroline; Loughlin, John; Mughal, Zulf; Ryan, Fiona; Shaw, Nick; Thakker, Yogini V; Tiosano, Dov; Nesbit, M Andrew; Thakker, Rajesh V

    2010-05-15

    GCMB is a member of the small transcription factor family GCM (glial cells missing), which are important regulators of development, present in vertebrates and some invertebrates. In man, GCMB encodes a 506 amino acid parathyroid gland-specific protein, mutations of which have been reported to cause both autosomal dominant and autosomal recessive hypoparathyroidism. We ascertained 18 affected individuals from 12 families with autosomal recessive hypoparathyroidism and have investigated them for GCMB abnormalities. Four different homozygous germline mutations were identified in eight families that originate from the Indian Subcontinent. These consisted of a novel nonsense mutation R39X; a missense mutation, R47L in two families; a novel missense mutation, R110W; and a novel frameshifting deletion, I298fsX307 in four families. Haplotype analysis, using polymorphic microsatellites from chromosome 6p23-24, revealed that R47L and I298fsX307 mutations arose either as ancient founders, or recurrent de novo mutations. Functional studies including: subcellular localization studies, EMSAs and luciferase-reporter assays, were undertaken and these demonstrated that: the R39X mutant failed to localize to the nucleus; the R47L and R110W mutants both lost DNA-binding ability; and the I298fsX307 mutant had reduced transactivational ability. In order to gain further insights, we undertook 3D-modeling of the GCMB DNA-binding domain, which revealed that the R110 residue is likely important for the structural integrity of helix 2, which forms part of the GCMB/DNA binding interface. Thus, our results, which expand the spectrum of hypoparathyroidism-associated GCMB mutations, help elucidate the molecular mechanisms underlying DNA-binding and transactivation that are required for this parathyroid-specific transcription factor.

  11. Global gene expression analysis and regulation of the principal genes expressed in bovine placenta in relation to the transcription factor AP-2 family

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    Kizaki Keiichiro

    2007-04-01

    Full Text Available Abstract Background Cell-cell communication is an important factor in feto-maternal units during placentogenesis. The placenta produces pivotal hormones and cytokines for communication between cotyledonary villi and the maternal caruncle. Gene expression in bovine placenta throughout pregnancy was comprehensively screened by a cDNA microarray, and we searched for a common transcription factor in a gene cluster that showed increasing expression throughout gestation in cotyledonary villi and caruncle. Methods Placentomal tissues (villi and caruncle were collected from Day 25 to Day 250 of gestation for microarray analysis. Global gene expression profiles were analyzed using the k-means clustering method. A consensus sequence cis-element that may control up-regulated genes in a characteristic cluster was examined in silico. The quantitative expression and localization of a specific transcription factor were investigated in each tissue using quantitative real-time RT-PCR and in situ hybridization. Results The microarray expression profiles were classified into ten clusters. The genes with most markedly increased expression became concentrated in cluster 2 as gestation proceeded. Cluster 2 included placental lactogen (CSH1, pregnancy-associated glycoprotein-1 (PAG1, and sulfotransferase family 1E estrogen-preferring member 1 (SULT1E1, which were mainly detected in giant trophoblast binucleate cells (BNC. Consensus sequence analysis identified transcription factor AP-2 binding sites in some genes in this cluster. Quantitative real-time RT-PCR analysis confirmed that high level expression of transcription factor AP-2 alpha (TFAP2A was common to cluster 2 genes during gestation. In contrast, the expression level of another AP-2 family gene, transcription factor AP-2 beta (TFAP2B, was extremely low over the same period. Another gene of the family, transcription factor AP-2 gamma (TFAP2C, was expressed at medium level compared with TFAP2A and TFAP2B. In

  12. Two adjacent and similar TetR family transcriptional regulator genes, SAV577 and SAV576, co-regulate avermectin production in Streptomyces avermitilis.

    Science.gov (United States)

    Guo, Jia; Zhang, Xuan; Chen, Zhi; Wen, Ying; Li, Jilun

    2014-01-01

    Streptomyces avermitilis is an important bacterial species used for industrial production of avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR), as a downregulator of avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase) and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.

  13. Two adjacent and similar TetR family transcriptional regulator genes, SAV577 and SAV576, co-regulate avermectin production in Streptomyces avermitilis.

    Directory of Open Access Journals (Sweden)

    Jia Guo

    Full Text Available Streptomyces avermitilis is an important bacterial species used for industrial production of avermectins, a family of broad-spectrum anthelmintic agents. We previously identified the protein SAV576, a TetR family transcriptional regulator (TFR, as a downregulator of avermectin biosynthesis that acts by controlling transcription of its major target gene SAV575 (which encodes cytochrome P450/NADPH-ferrihemoprotein reductase and ave genes. SAV577, another TFR gene, encodes a SAV577 protein that displays high amino acid homology with SAV576. In this study, we examined the effect of SAV577 on avermectin production and the relationships between SAV576 and SAV577. SAV577 downregulated avermectin biosynthesis indirectly, similarly to SAV576. SAV576 and SAV577 both directly repressed SAV575 transcription, and reciprocally repressed each other's expression. SAV575 transcription levels in various S. avermitilis strains were correlated with avermectin production levels. DNase I footprinting and electrophoretic mobility shift assays indicated that SAV576 and SAV577 compete for the same binding regions, and that DNA-binding affinity of SAV576 is much stronger than that of SAV577. GST pull-down assays revealed no direct interaction between the two proteins. Taken together, these findings suggest that SAV577 regulates avermectin production in S. avermitilis by a mechanism similar to that of SAV576, and that the role of SAV576 is dominant over that of SAV577. This is the first report of two adjacent and similar TFR genes that co-regulate antibiotic production in Streptomyces.

  14. A Comprehensive Catalog of Human KRAB-associated Zinc Finger Genes: Insights into the Evolutionary History of a Large Family of Transcriptional Repressors

    Energy Technology Data Exchange (ETDEWEB)

    Huntley, S; Baggott, D M; Hamilton, A T; Tran-Gyamfi, M; Yang, S; Kim, J; Gordon, L; Branscomb, E; Stubbs, L

    2005-09-30

    Krueppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotic species. In mammals, most ZNF proteins comprise a single class of transcriptional repressors in which a chromatin interaction domain, called the Krueppel-associated box (KRAB) is attached to a tandem array of DNA-binding zinc-finger motifs. KRAB-ZNF loci are specific to tetrapod vertebrates, but have expanded dramatically in numbers through repeated rounds of segmental duplication to create a gene family with hundreds of members in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the human genome for key motifs and used them to construct and manually curate gene models. The resulting KRAB-ZNF gene catalog includes 326 known genes, 243 of which were structurally corrected by manual annotation, and 97 novel KRAB-ZNF genes; this single family therefore comprises 20% of all predicted human transcription factor genes. Many of the genes are alternatively spliced, yielding a total of 743 distinct predicted proteins. Although many human KRAB-ZNF genes are conserved in mammals, at least 136 and potentially more than 200 genes of this type are primate-specific including many recent segmental duplicates. KRAB-ZNF genes are active in a wide variety of human tissues suggesting roles in many key biological processes, but most member genes remain completely uncharacterized. Because of their sheer numbers, wide-ranging tissue-specific expression patterns, and remarkable evolutionary divergence we predict that KRAB-ZNF transcription factors have played critical roles in crafting many aspects of human biology, including both deeply conserved and primate-specific traits.

  15. A special member of the rice SRO family, OsSRO1c, mediates responses to multiple abiotic stresses through interaction with various transcription factors.

    Science.gov (United States)

    You, Jun; Zong, Wei; Du, Hao; Hu, Honghong; Xiong, Lizhong

    2014-04-01

    SIMILAR TO RCD ONE (SRO) is a plant-specific gene family involved in development and abiotic stress responses. SRO proteins are characterized by containing poly (ADP-ribose) polymerase catalytic (PARP) and C-terminal RCD1-SRO-TAF4 domains, and can be classified into two groups and five subgroups on the basis of their PARP domain. Expression analysis of rice SRO genes in response to various abiotic stresses showed that OsSRO1c, a rice SRO gene which functions downstream of the stress-responsive transcription factor SNAC1, is the major stress-responsive gene in the rice SRO family. The ossro1c-1 mutant showed resistance not only to chloroplastic oxidative stress, but also to apoplastic oxidative stress. However, the ossro1c-1 mutant and artificial microRNA-OsSRO1c transgenic rice were significantly impaired in cold tolerance. When compared with the well-characterized Arabidopsis SRO protein radical-induced cell death 1 (RCD1), OsSRO1c has considerable variation in the protein sequence, and the two genes exhibit different expression profiles under abiotic stresses. Furthermore, ossro1c-1 and rcd1 showed different responses to multiple abiotic stresses. By screening an Arabidopsis transcription factor library, 29 transcription factors interacted with OsSRO1c in yeast, but only two of these transcription factors were reported to interact with RCD1, which may partly explain the different responses of the two mutants under various stresses. The data presented in this report provide important clues for further elucidating the molecular and biochemical mechanisms of OsSRO1c in mediating responses to multiple abiotic stresses.

  16. Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R

    NARCIS (Netherlands)

    Passtoors, W.M.; Boer, J.M.; Goeman, J.G.; Van den Akker, E.B.; Deelen, J.; Zwaan, B.J.; Scarborough, A.; Van der Breggen, R.; Vossen, R.H.A.M.; et al.

    2012-01-01

    The Leiden Longevity Study consists of families that express extended survival across generations, decreased morbidity in middle-age, and beneficial metabolic profiles. To identify which pathways drive this complex phenotype of familial longevity and healthy aging, we performed a genome-wide gene ex

  17. Quantitative RT-PCR based platform for rapid quantification of the transcripts of highly homologous multigene families and their members during grain development.

    Science.gov (United States)

    Kaczmarczyk, Agnieszka; Bowra, Steve; Elek, Zoltan; Vincze, Eva

    2012-10-09

    Cereal storage proteins represent one of the most important sources of protein for food and feed and they are coded by multigene families. The expression of the storage protein genes exhibits a temporal fluctuation but also a response to environmental stimuli. Analysis of temporal gene expression combined with genetic variation in large multigene families with high homology among the alleles is very challenging. We designed a rapid qRT-PCR system with the aim of characterising the variation in the expression of hordein genes families. All the known D-, C-, B-, and γ-hordein sequences coding full length open reading frames were collected from commonly available databases. Phylogenetic analysis was performed and the members of the different hordein families were classified into subfamilies. Primer sets were designed to discriminate the gene expression level of whole families, subfamilies or individual members. The specificity of the primer sets was validated before successfully applying them to a cDNA population derived from developing grains of field grown Hordeum vulgare cv. Barke. The results quantify the number of moles of transcript contributed to a particular gene family and its subgroups. More over the results indicate the genotypic specific gene expression. Quantitative RT-PCR with SYBR Green labelling can be a useful technique to follow gene expression levels of large gene families with highly homologues members. We showed variation in the temporal expression of genes coding for barley storage proteins. The results imply that our rapid qRT-PCR system was sensitive enough to identify the presence of alleles and their expression profiles. It can be used to check the temporal fluctuations in hordein expressions or to find differences in their response to environmental stimuli. The method could be extended for cultivar recognition as some of the sequences from the database originated from cv. Golden Promise were not expressed in the studied barley cultivar

  18. Transcriptional differences in gene families of the ascorbate-glutathione cycle in wheat during mild water deficit.

    Science.gov (United States)

    Secenji, Maria; Hideg, Eva; Bebes, Attila; Györgyey, János

    2010-01-01

    When comparing the responses of two wheat (Triticum aestivum L.) genotypes, the drought-tolerant Plainsman V and the drought-sensitive Cappelle Desprez, to reduced amounts of irrigation water, we found differences in ascorbate metabolism: both ascorbate oxidation and transcription levels of enzymes processing ascorbate were changed. Relative transcript levels of ascorbate peroxidase (APX), monodehydroascorbate reductase (MDAR), dehydroascorbate reductase (DHAR) and glutathione reductase (GR) isoenzymes, predicted to localize in distinct subcellular organelles, showed different transcriptional changes in the two genotypes. Among APX coding mRNAs, expression levels of two cytosolic (cAPX I, II) and a thylakoid-bound (tAPX) variants increased significantly in Plainsman V while a cytosolic (cAPX I) and a stromal (sAPX II) APX coding transcripts were found to be higher in Cappelle Desprez after a 4-week-long water-deficit stress. Examining the MDARs, two cytosolic isoforms (cMDAR I, II) displayed significant up-regulation of mRNA levels in the sensitive genotype, whereas only one of them (cMDAR II) did in the tolerant cultivar. We found an up-regulated chloroplastic DHAR (chlDHAR) mRNA only in the sensitive Cappelle Desprez. However, increased expression levels of a cytosolic GR (cGR) and a chloroplastic GR (chlGR) were detected only in the tolerant Plainsman V. After 4 weeks of reduced irrigation, a significantly lower ascorbate/dehydroascorbate ratio was detected in leaves of the sensitive Cappelle Desprez than in the tolerant Plainsman V. Our results indicate that more robust transcription of ascorbate-based detoxification machinery may prevent an adverse shift of the cellular redox balance.

  19. Genome-Wide Analysis of the AP2/ERF Transcription Factors Family and the Expression Patterns of DREB Genes in Moso Bamboo (Phyllostachys edulis).

    Science.gov (United States)

    Wu, Huili; Lv, Hao; Li, Long; Liu, Jun; Mu, Shaohua; Li, Xueping; Gao, Jian

    2015-01-01

    The AP2/ERF transcription factor family, one of the largest families unique to plants, performs a significant role in terms of regulation of growth and development, and responses to biotic and abiotic stresses. Moso bamboo (Phyllostachys edulis) is a fast-growing non-timber forest species with the highest ecological, economic and social values of all bamboos in Asia. The draft genome of moso bamboo and the available genomes of other plants provide great opportunities to research global information on the AP2/ERF family in moso bamboo. In total, 116 AP2/ERF transcription factors were identified in moso bamboo. The phylogeny analyses indicated that the 116 AP2/ERF genes could be divided into three subfamilies: AP2, RAV and ERF; and the ERF subfamily genes were divided into 11 groups. The gene structures, exons/introns and conserved motifs of the PeAP2/ERF genes were analyzed. Analysis of the evolutionary patterns and divergence showed the PeAP2/ERF genes underwent a large-scale event around 15 million years ago (MYA) and the division time of AP2/ERF family genes between rice and moso bamboo was 15-23 MYA. We surveyed the putative promoter regions of the PeDREBs and showed that largely stress-related cis-elements existed in these genes. Further analysis of expression patterns of PeDREBs revealed that the most were strongly induced by drought, low-temperature and/or high salinity stresses in roots and, in contrast, most PeDREB genes had negative functions in leaves under the same respective stresses. In this study there were two main interesting points: there were fewer members of the PeDREB subfamily in moso bamboo than in other plants and there were differences in DREB gene expression profiles between leaves and roots triggered in response to abiotic stress. The information produced from this study may be valuable in overcoming challenges in cultivating moso bamboo.

  20. Mechanism of action of the Escherichia coli phage shock protein PspA in repression of the AAA family transcription factor PspF.

    Science.gov (United States)

    Elderkin, Sarah; Jones, Susan; Schumacher, Jörg; Studholme, David; Buck, Martin

    2002-06-28

    The PspA protein, a negative regulator of the Escherichia coli phage shock psp operon, is produced when virulence factors are exported through secretins in many Gram-negative pathogenic bacteria and its homologue in plants, VIPP1, plays a critical role in thylakoid biogenesis, essential for photosynthesis. Activation of transcription by the enhancer-dependent bacterial sigma(54) containing RNA polymerase occurs through ATP hydrolysis-driven protein conformational changes enabled by activator proteins that belong to the large AAA(+) mechanochemical protein family. We show that PspA directly and specifically acts upon and binds to the AAA(+) domain of the PspF transcription activator. Interactions involving PspF and nucleotide are changed by the action of PspA. These changes and the complexes that form between PspF and PspA can explain how PspA exerts its negative effects upon transcription activated by PspF, and are of significance when considering how activities of other AAA(+) proteins might be controlled.

  1. Mechanistic Heterogeneity in Site Recognition by the Structurally Homologous DNA-binding Domains of the ETS Family Transcription Factors Ets-1 and PU.1*

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H.; Munde, Manoj; Carvalho, Victor D.; Wilson, W. David; Poon, Gregory M. K.

    2014-01-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a “dry” mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1·DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. PMID:24952944

  2. A Zinc-Finger-Family Transcription Factor, AbVf19, Is Required for the Induction of a Gene Subset Important for Virulence in Alternaria brassicicola

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Akhil [Univ. of Hawaii, Manoa, HI (United States); Ohm, Robin A. [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Oxiles, Lindsay [Univ. of Hawaii, Manoa, HI (United States); Brooks, Fred [Univ. of Hawaii, Manoa, HI (United States); Lawrence, Christopher B. [Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States); Grigoriev, Igor V. [USDOE Joint Genome Inst., Walnut Creek, CA (United States); Cho, Yangrae [Univ. of Hawaii, Manoa, HI (United States)

    2011-10-26

    Alternaria brassicicola is a successful saprophyte and necrotrophic plant pathogen with a broad host range within the family Brassicaceae. It produces secondary metabolites that marginally affect virulence. Cell wall degrading enzymes (CDWE) have been considered important for pathogenesis but none of them individually have been identified as significant virulence factors in A. brassicicola. In this study, knockout mutants of a gene, AbVf19, were created and produced considerably smaller lesions than the wild type on inoculated host plants. The presence of tandem zinc-finger domains in the predicted amino acid sequence and nuclear localization of AbVf19- reporter protein suggested that it was a transcription factor. Gene expression comparisons using RNA-seq identified 74 genes being downregulated in the mutant during a late stage of infection. Among the 74 downregulated genes, 28 were putative CWDE genes. These were hydrolytic enzyme genes that composed a small fraction of genes within each family of cellulases, pectinases, cutinases, and proteinases. The mutants grew slower than the wild type on an axenic medium with pectin as a major carbon source. This study demonstrated the existence and the importance of a transcription factor that regulates a suite of genes that are important for decomposing and utilizing plant material during the late stage of plant infection.

  3. Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7).

    Science.gov (United States)

    Sundqvist, Anders; Bengoechea-Alonso, Maria T; Ye, Xin; Lukiyanchuk, Vasyl; Jin, Jianping; Harper, J Wade; Ericsson, Johan

    2005-06-01

    The sterol regulatory element binding protein (SREBP) family of transcription factors controls cholesterol and lipid metabolism. The nuclear forms of these proteins are rapidly degraded by the ubiquitin-proteasome pathway, but the signals and factors required for this are unknown. Here, we identify a phosphodegron in SREBP1a that serves as a recognition motif for the SCF(Fbw7) ubiquitin ligase. Fbw7 interacts with nuclear SREBP1a and enhances its ubiquitination and degradation in a manner dependent on the phosphorylation of T426 and S430 by GSK-3. Fbw7 also degrades nuclear SREBP1c and SREBP2, and inactivation of endogenous Fbw7 results in stabilization of nuclear SREBP1 and -2, enhanced expression of SREBP target genes, enhanced synthesis of cholesterol and fatty acids, and enhanced receptor-mediated uptake of LDL. Thus, our results suggest that Fbw7 may be a major regulator of lipid metabolism through control of the phosphorylation-dependent degradation of the SREBP family of transcription factors.

  4. Characterization and phylogenetic analysis of Krüppel-like transcription factor (KLF) gene family in tree shrews (Tupaia belangeri chinensis).

    Science.gov (United States)

    Shao, Ming; Ge, Guang-Zhe; Liu, Wen-Jing; Xiao, Ji; Xia, Hou-Jun; Fan, Yu; Zhao, Feng; He, Bao-Li; Chen, Ceshi

    2016-12-10

    Krüppel-like factors (KLFs) are a family of zinc finger transcription factors regulating embryonic development and diseases. The phylogenetics of KLFs has not been studied in tree shrews, an animal lineage with a closer relationship to primates than rodents. Here, we identified 17 KLFs from Chinese tree shrew (Tupaia belangeri chinensis). KLF proteins are highly conserved among humans, monkeys, rats, mice and tree shrews compared to zebrafish and chickens. The CtBP binding site, Sin3A binding site and nuclear localization signals are largely conserved between tree shrews and human beings. Tupaia belangeri (Tb) KLF5 contains several conserved post-transcriptional modification motifs. Moreover, the mRNA and protein expression patterns of multiple tbKLFs are tissue-specific . TbKLF5, like hKLF5, significantly promotes NIH3T3 cell proliferation in vitro. These results provide insight for future studies regarding the structure and function of the tbKLF gene family.

  5. Genomic cartography and proposal of nomenclature for the repeated, interspersed elements of the Leishmania major SIDER2 family and identification of SIDER2-containing transcripts.

    Science.gov (United States)

    Requena, Jose M; Rastrojo, Alberto; Garde, Esther; López, Manuel C; Thomas, M Carmen; Aguado, Begoña

    2017-03-01

    The genomes of most eukaryotic organisms contain a large number of transposable elements that are able to move from one genomic site to another either by transferring of DNA mobile elements (transposons) or transpose via reverse transcription of an RNA intermediate (retroposons). An exception to this rule is found in protists of the subgenus Leishmania, in which active retroposons degenerated after a flourishing era, leaving only retroposon remains; these have been classified into two families: SIDER1 and SIDER2. In this work, we have re-examined the elements belonging to the family SIDER2 present in the genome of Leishmania major with the aim of providing a nomenclature that will facilitate a future reference to particular elements. According to sequence conservation, the 1100 SIDER2 elements have been grouped into subfamilies, and the inferred taxonomic relationships have also been incorporated into the nomenclature. Additionally, we are providing detailed data regarding the genomic distribution of these elements and their association with specific transcripts, based on the recently established transcriptome for L. major. Thus, the presented data can help to study and better understand the roles played by these degenerated retroposons in both regulation of gene expression and genome plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Differential expression of ETS family transcription factors in NCCIT human embryonic carcinoma cells upon retinoic acid-induced differentiation.

    Science.gov (United States)

    Park, Sung-Won; Do, Hyun-Jin; Ha, Woo Tae; Han, Mi-Hee; Song, Hyuk; Uhm, Sang-Jun; Chung, Hak-Jae; Kim, Jae-Hwan

    2014-01-01

    E26 transformation-specific (ETS) transcription factors play important roles in normal and tumorigenic processes during development, differentiation, homeostasis, proliferation, and apoptosis. To identify critical ETS factor(s) in germ cell-derived cancer cells, we examined the expression patterns of the 27 ETS transcription factors in naive and differentiated NCCIT human embryonic carcinoma cells, which exhibit both pluripotent and tumorigenic characteristics. Overall, expression of ETS factors was relatively low in NCCIT cells. Among the 27 ETS factors, polyomavirus enhancer activator 3 (PEA3) and epithelium-specific ETS transcription factor-1 (ESE-1) exhibited the most significant changes in their expression levels. Western blot analysis confirmed these patterns, revealing reduced levels of PEA3 protein and elevated levels of ESE-1 protein in differentiated cells. PEA3 increased the proportion of cells in S-phase and promoted cell growth, whereas ESE-1 reduced proliferation potential. These data suggest that PEA3 and ESE-1 may play important roles in pluripotent and tumorigenic embryonic carcinoma cells. These findings contribute to our understanding of the functions of oncogenic ETS factors in germ cell-derived stem cells during processes related to tumorigenesis and pluripotency.

  7. Functional interplay of SP family members and nuclear factor Y is essential for transcriptional activation of the human Calreticulin gene.

    Science.gov (United States)

    Schardt, Julian A; Keller, Manuela; Seipel, Katja; Pabst, Thomas

    2015-09-01

    Calreticulin (CALR) is a highly conserved, multifunctional protein involved in a variety of cellular processes including the maintenance of intracellular calcium homeostasis, proper protein folding, differentiation and immunogenic cell death. More recently, a crucial role for CALR in the pathogenesis of certain hematologic malignancies was discovered: in clinical subgroups of acute myeloid leukemia, CALR overexpression mediates a block in differentiation, while somatic mutations have been found in the majority of patients with myeloproliferative neoplasms with nonmutated Janus kinase 2 gene (JAK2) or thrombopoietin receptor gene (MPL). However, the mechanisms underlying CALR promoter activation have insufficiently been investigated so far. By dissecting the core promoter region, we could identify a functional TATA-box relevant for transcriptional activation. In addition, we characterized two evolutionary highly conserved cis-regulatory modules (CRMs) within the proximal promoter each composed of one binding site for the transcription factors SP1 and SP3 as well as for the nuclear transcription factor Y (NFY) and we verified binding of these factors to their cognate sites in vitro and in vivo.

  8. Jeb/Alk signalling regulates the Lame duck GLI family transcription factor in the Drosophila visceral mesoderm.

    Science.gov (United States)

    Popichenko, Dmitry; Hugosson, Fredrik; Sjögren, Camilla; Dogru, Murat; Yamazaki, Yasuo; Wolfstetter, Georg; Schönherr, Christina; Fallah, Mahsa; Hallberg, Bengt; Nguyen, Hanh; Palmer, Ruth H

    2013-08-01

    The Jelly belly (Jeb)/Anaplastic Lymphoma Kinase (Alk) signalling pathway regulates myoblast fusion in the circular visceral mesoderm (VM) of Drosophila embryos via specification of founder cells. However, only a limited number of target molecules for this pathway are described. We have investigated the role of the Lame Duck (Lmd) transcription factor in VM development in relationship to Jeb/Alk signal transduction. We show that Alk signalling negatively regulates Lmd activity post-transcriptionally through the MEK/MAPK (ERK) cascade resulting in a relocalisation of Lmd protein from the nucleus to cytoplasm. It has previously been shown that downregulation of Lmd protein is necessary for the correct specification of founder cells. In the visceral mesoderm of lmd mutant embryos, fusion-competent myoblasts seem to be converted to 'founder-like' cells that are still able to build a gut musculature even in the absence of fusion. The ability of Alk signalling to downregulate Lmd protein requires the N-terminal 140 amino acids, as a Lmd(141-866) mutant remains nuclear in the presence of active ALK and is able to drive robust expression of the Lmd downstream target Vrp1 in the developing VM. Our results suggest that Lmd is a target of Jeb/Alk signalling in the VM of Drosophila embryos.

  9. Transcription factor 7-like 2 (TCF7L2 variant is associated with familial breast cancer risk: a case-control study

    Directory of Open Access Journals (Sweden)

    Schmutzler Rita K

    2006-11-01

    Full Text Available Abstract Background The transcription factor 7-like 2 (TCF7L2 is a critical component of the Wnt/β-catenin pathway. Aberrant TCF7L2 expression modifies Wnt signaling and mediates oncogenic effects through the upregulation of c-MYC and cyclin D. Genetic alterations in TCF7L2 may therefore affect cancer risk. Recently, TCF7L2 variants, including the microsatellite marker DG10S478 and the nearly perfectly linked SNP rs12233372, were identified to associate with type 2 diabetes. Methods We investigated the effect of the TCF7L2 rs12255372 variant on familial breast cancer (BC risk by means of TaqMan allelic discrimination, analyzing BRCA1/2 mutation-negative index patients of 592 German BC families and 735 control individuals. Results The T allele of rs12255372 showed an association with borderline significance (OR = 1.19, 95% C.I. = 1.01-1.42, P = 0.04, and the Cochran-Armitage test for trend revealed an allele dose-dependent association of rs12255372 with BC risk (Ptrend = 0.04. Conclusion Our results suggest a possible influence of TCF7L2 rs12255372 on the risk of familial BC.

  10. Differential effects of the HESR/HEY transcription factor family on dopamine transporter reporter gene expression via variable number of tandem repeats.

    Science.gov (United States)

    Kanno, Kouta; Ishiura, Shoichi

    2011-04-01

    The 3'-untranslated region (UTR) of the human dopamine transporter (DAT1) gene contains a variable number of tandem repeats (VNTR) domain, which is thought to be associated with dopamine-related psychiatric disorders, personality, and behavior. However, the molecular and neuronal functions of polymorphisms within the VNTR domain are unknown. We previously identified the transcription factor HESR1 (HEY1) as a VNTR-binding protein. Hesr1 knockout mice exhibit DAT up-regulation in the brain and low levels of spontaneous activity. Other members of the HESR (HEY) family, including HESR2 (HEY2) and 3 (HEYL), have similar DNA-binding domains. In this study, we analyzed the effects of HESR1, -2, and -3 on DAT1 expression in human neuroblastoma SH-SY5Y cells using luciferase reporter assays. We found that the VNTR domain played an inhibitory role in DAT1 reporter gene expression and that HESR1 and -2 inhibited expression via both the core promoter and the VNTR. The inhibitory effects of HESR family members on DAT reporter gene expression differed depending on the number of repeats in the VNTR domain. We also found that each Hesr was expressed in the dopaminergic neurons in the mouse midbrain. These results suggest that the HESR family is involved in DAT expression via the VNTR domain.

  11. Members of miR-169 family are induced by high salinity and transiently inhibit the NF-YA transcription factor

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    Lin Hongxuan

    2009-04-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are endogenously expressed small RNAs with a length of about 21 nt. MiRNAs silence their target genes at the post-transcriptional level. In plants, miRNAs play various developmental and physiological roles by cleavaging mRNAs predominantly. Drought and high salinity are the most severe environmental abiotic stresses and cause crop losses all over the world. Results In this study, we identified miR-169g and miR-169n (o as high salinity-responsive miRNAs in rice. MiR-169n and miR169o were in a miRNA cluster with a distance of 3707 base pairs (bp. The high degree of conservation and close phylogenic distance of pre-miR-169n and pre-miR-169o indicated that they were derived from a very recent tandem duplication evolutionary event. The existence of a cis-acting abscisic acid responsive element (ABRE in the upstream region of miR-169n (o suggested that miR-169n (o may be regulated by ABA. In our previous study, we found that miR-169g was induced by the osmotic stress caused by drought via a dehydration-responsive element (DRE. Thus, our data showed that there were both overlapping and distinct responses of the miR-169 family to drought and salt stresses. We also showed that these miR-169 members selectively cleaved one of the NF-YA genes, Os03g29760, which is a CCAAT-box binding transcription factor and participates in transcriptional regulation of large number genes. Finally, we found one or more ath-miR-169 member that was also induced by high salinity. Conclusion We identified members of the miR-169 family as salt-induced miRNAs and analyzed their evolution, gene organization, expression, transcriptional regulation motif and target gene. Our data also indicated that the salt-induction of some miR-169 members was a general property in plants.

  12. Members of miR-169 family are induced by high salinity and transiently inhibit the NF-YA transcription factor.

    Science.gov (United States)

    Zhao, Botao; Ge, Liangfa; Liang, Ruqiang; Li, Wei; Ruan, Kangcheng; Lin, Hongxuan; Jin, Youxin

    2009-04-08

    MicroRNAs (miRNAs) are endogenously expressed small RNAs with a length of about 21 nt. MiRNAs silence their target genes at the post-transcriptional level. In plants, miRNAs play various developmental and physiological roles by cleavaging mRNAs predominantly. Drought and high salinity are the most severe environmental abiotic stresses and cause crop losses all over the world. In this study, we identified miR-169g and miR-169n (o) as high salinity-responsive miRNAs in rice. MiR-169n and miR169o were in a miRNA cluster with a distance of 3707 base pairs (bp). The high degree of conservation and close phylogenic distance of pre-miR-169n and pre-miR-169o indicated that they were derived from a very recent tandem duplication evolutionary event. The existence of a cis-acting abscisic acid responsive element (ABRE) in the upstream region of miR-169n (o) suggested that miR-169n (o) may be regulated by ABA. In our previous study, we found that miR-169g was induced by the osmotic stress caused by drought via a dehydration-responsive element (DRE). Thus, our data showed that there were both overlapping and distinct responses of the miR-169 family to drought and salt stresses. We also showed that these miR-169 members selectively cleaved one of the NF-YA genes, Os03g29760, which is a CCAAT-box binding transcription factor and participates in transcriptional regulation of large number genes. Finally, we found one or more ath-miR-169 member that was also induced by high salinity. We identified members of the miR-169 family as salt-induced miRNAs and analyzed their evolution, gene organization, expression, transcriptional regulation motif and target gene. Our data also indicated that the salt-induction of some miR-169 members was a general property in plants.

  13. Comprehensive analysis of SAUR gene family in citrus and its transcriptional correlation with fruitlet drop from abscission zone A.

    Science.gov (United States)

    Xie, Rangjin; Dong, Cuicui; Ma, Yanyan; Deng, Lie; He, Shaolan; Yi, Shilai; Lv, Qiang; Zheng, Yongqiang

    2015-11-01

    Small auxin-up RNA (SAUR) gene family is large, and the members of which can be rapidly induced by auxin and encode highly unstable mRNAs. SAUR genes are involved in various developmental and physiological processes, such as leaf senescence, fruitlet abscission, and hypocotyl development. However, their modes of action in citrus remain unknown. Hereby, a systematic analysis of SAUR gene family in citrus was conducted through a genome-wide search. In this study, a total of 70 SAUR genes, referred to as CitSAURs, have been identified in citrus. The evolutionary relationship and the intro-exon organization were analyzed, revealing strong gene conservation and the expansion of particular functional genes during plant evolution. Expression analysis showed that the major of CitSAUR genes were expressed in at least one tissue and showed distinctive expression levels, indicating the SAUR gene family play important roles in the development and growth of citrus organs. However, there were more than 20 CitSAUR genes such as CitSARU36, CitSAUR37, and CitSAUR54 exhibiting very low expression level in all tissue tested. Twenty-three out of 70 CitSAUR genes were responded to indole-3-acetic acid (IAA) treatment, of which just CitSAUR19 was down-regulated. Additionally, 14 CitSAUR genes exhibited distinct changes during fruitlet abscission, however just 5 of them including CitSAUR06, CitSAUR08, CitSAUR44, CitSAUR61, and CitSAUR64 were associated with fruitlet abscission. The current study provides basic information for the citrus SAUR gene family and will pave the way for deciphering the precise role of SAURs in citrus development and growth as well as fruitlet abscission.

  14. Clustered organization and transcriptional analysis of a family of five csp genes of Lactococcus lactis MG1363

    NARCIS (Netherlands)

    Wouters, Jeroen A.; Sanders, Jan-Willem; Kok, Jan; Vos, Willem M. de; Kuipers, Oscar P.; Abee, Tjakko; Wouters, J.W.

    1998-01-01

    A family of genes encoding cold-shock proteins, named cspA, cspB, cspC, cspD and cspE, was cloned and sequenced from Lactococcus lactis MG1363. The genes cspA and cspB and the genes cspC and cspD are located in tandem repeats, an organization of csp genes that has never been encountered before. The

  15. Crystal structure and DNA binding activity of a PadR family transcription regulator from hypervirulent Clostridium difficile R20291.

    Science.gov (United States)

    Isom, Catherine E; Menon, Smita K; Thomas, Leonard M; West, Ann H; Richter-Addo, George B; Karr, Elizabeth A

    2016-10-04

    Clostridium difficile is a spore-forming obligate anaerobe that can remain viable for extended periods, even in the presence of antibiotics, which contributes to the persistence of this bacterium as a human pathogen during host-to-host transmission and in hospital environments. We examined the structure and function of a gene product with the locus tag CDR20291_0991 (cdPadR1) as part of our broader goal aimed at elucidating transcription regulatory mechanisms involved in virulence and antibiotic resistance of the recently emergent hypervirulent C. difficile strain R20291. cdPadR1 is genomically positioned near genes that are involved in stress response and virulence. In addition, it was previously reported that cdPadR1 and a homologue from the historical C. difficile strain 630 (CD630_1154) were differentially expressed when exposed to stressors, including antibiotics. The crystal structure of cdPadR1 was determined to 1.9 Å resolution, which revealed that it belongs to the PadR-s2 subfamily of PadR transcriptional regulators. cdPadR1 binds its own promoter and other promoter regions from within the C. difficile R20291 genome. DNA binding experiments demonstrated that cdPadR1 binds a region comprised of inverted repeats and an AT-rich core with the predicted specific binding motif, GTACTAT(N2)ATTATA(N)AGTA, within its own promoter that is also present in 200 other regions in the C. difficile R20291 genome. Mutation of the highly conserved W in α4 of the effector binding/oligomerization domain, which is predicted to be involved in multi-drug recognition and dimerization in other PadR-s2 proteins, resulted in alterations of cdPadR1 binding to the predicted binding motif, potentially due to loss of higher order oligomerization. Our results indicate that cdPadR1 binds a region within its own promoter consisting of the binding motif GTACTAT(N2)ATTATA(N)AGTA and seems to associate non-specifically with longer DNA fragments in vitro, which may facilitate promoter and

  16. 1.65 Å resolution structure of the AraC-family transcriptional activator ToxT from Vibrio cholerae.

    Science.gov (United States)

    Li, Jiaqin; Wehmeyer, Graham; Lovell, Scott; Battaile, Kevin P; Egan, Susan M

    2016-09-01

    ToxT is an AraC-family transcriptional activator protein that controls the expression of key virulence factors in Vibrio cholerae, the causative agent of cholera. ToxT directly activates the expression of the genes that encode the toxin-coregulated pilus and cholera toxin, and also positively auto-regulates its own expression from the tcp promoter. The crystal structure of ToxT has previously been solved at 1.9 Å resolution (PDB entry 3gbg). In this study, a crystal structure of ToxT at 1.65 Å resolution with a similar overall structure to the previously determined structure is reported. However, there are distinct differences between the two structures, particularly in the region that extends from Asp101 to Glu110. This region, which can influence ToxT activity but was disordered in the previous structure, can be traced entirely in the current structure.

  17. Genome-Wide Analysis of the AP2/ERF Transcription Factors Family and the Expression Patterns of DREB Genes in Moso Bamboo (Phyllostachys edulis)

    Science.gov (United States)

    Li, Long; Liu, Jun; Mu, Shaohua; Li, Xueping; Gao, Jian

    2015-01-01

    The AP2/ERF transcription factor family, one of the largest families unique to plants, performs a significant role in terms of regulation of growth and development, and responses to biotic and abiotic stresses. Moso bamboo (Phyllostachys edulis) is a fast-growing non-timber forest species with the highest ecological, economic and social values of all bamboos in Asia. The draft genome of moso bamboo and the available genomes of other plants provide great opportunities to research global information on the AP2/ERF family in moso bamboo. In total, 116 AP2/ERF transcription factors were identified in moso bamboo. The phylogeny analyses indicated that the 116 AP2/ERF genes could be divided into three subfamilies: AP2, RAV and ERF; and the ERF subfamily genes were divided into 11 groups. The gene structures, exons/introns and conserved motifs of the PeAP2/ERF genes were analyzed. Analysis of the evolutionary patterns and divergence showed the PeAP2/ERF genes underwent a large-scale event around 15 million years ago (MYA) and the division time of AP2/ERF family genes between rice and moso bamboo was 15–23 MYA. We surveyed the putative promoter regions of the PeDREBs and showed that largely stress-related cis-elements existed in these genes. Further analysis of expression patterns of PeDREBs revealed that the most were strongly induced by drought, low-temperature and/or high salinity stresses in roots and, in contrast, most PeDREB genes had negative functions in leaves under the same respective stresses. In this study there were two main interesting points: there were fewer members of the PeDREB subfamily in moso bamboo than in other plants and there were differences in DREB gene expression profiles between leaves and roots triggered in response to abiotic stress. The information produced from this study may be valuable in overcoming challenges in cultivating moso bamboo. PMID:25985202

  18. PrhN, a putative marR family transcriptional regulator, is involved in positive regulation of type III secretion system and full virulence of Ralstonia solanacearum

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    Zhang eYong

    2015-04-01

    Full Text Available The MarR-family of transcriptional regulators are involved in various cellular processes, including resistance to multiple antibiotics and other toxic chemicals, adaptation to different environments and pathogenesis in many plant and animal pathogens. Here, we reported a new MarR regulator PrhN, which was involved in the pathogenesis of Ralstonia solanacearum. prhN mutant exhibited significantly reduced virulence and stem colonization compared to that of wild type in tomato plants. prhN mutant caused identical hypersensitive response (HR on resistant plants to the wild type. Deletion of prhN gene substantially reduced the expression of type III secretion system (T3SS in vitro and in planta (mainly in tomato plants, which is essential for pathogenicity of R. solanacearum, and the complemented PrhN could restore its virulence and T3SS expression to that of wild type. T3SS is directly controlled by AraC-type transcriptional regulator HrpB, and the transcription of hrpB is activated by HrpG and PrhG. HrpG and PrhG are homologues but are regulated by the PhcA positively and negatively respectively. Deletion of prhN gene also abolished the expression of hrpB and prhG, but didn't change the expression of hrpG and phcA. Together, these results indicated that PrhN positively regulates T3SS expression through PrhG and HrpB. PrhN and PhcA should regulate prhG expression in a parallel way. This is the first report on the pathogenesis of MarR regulator in R. solanacearum, and this new finding will improve our understanding on the various biological functions of MarR regulator and the complex regulatory network on hrp regulon in R. solanacearum.

  19. Mechanistic heterogeneity in site recognition by the structurally homologous DNA-binding domains of the ETS family transcription factors Ets-1 and PU.1.

    Science.gov (United States)

    Wang, Shuo; Linde, Miles H; Munde, Manoj; Carvalho, Victor D; Wilson, W David; Poon, Gregory M K

    2014-08-01

    ETS family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in terms of the role of hydration and counter ion release. The data suggest two distinct mechanisms wherein Ets-1 follows a "dry" mechanism that rapidly parses sites through electrostatic interactions and direct protein-DNA contacts, whereas PU.1 utilizes hydration to interrogate sequence-specific sites and form a long-lived complex relative to the Ets-1 counterpart. The kinetic persistence of the high affinity PU.1 · DNA complex may be relevant to an emerging role of PU.1, but not Ets-1, as a pioneer transcription factor in vivo. In addition, PU.1 activity is critical to the development and function of macrophages and lymphocytes, which present osmotically variable environments, and hydration-dependent specificity may represent an important regulatory mechanism in vivo, a hypothesis that finds support in gene expression profiles of primary murine macrophages. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Directory of Open Access Journals (Sweden)

    Teresa Milano

    2016-01-01

    Full Text Available The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average that is homologous to fold type-I pyridoxal 5′-phosphate (PLP dependent enzymes like aspartate aminotransferase (AAT. These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs. Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups.

  1. Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family.

    Science.gov (United States)

    Stewart, A F; Richard, C W; Suzow, J; Stephan, D; Weremowicz, S; Morton, C C; Adra, C N

    1996-10-01

    Transcriptional Enhancer Factor-1 (TEF-1) is a transcription factor required for cardiac muscle gene activation. Since ablation of TEF-1 does not abolish cardiac gene expression, we sought to identify a human gene related to TEF-1 (RTEF-1) that might also participate in cardiac gene regulation. A human heart cDNA library was screened to obtain a full-length RTEF-1 cDNA. Fluorescence in situ hybridization assigned the RTEF-1 gene to chromosome 12p13.2-p13.3. In contrast, PCR screening of human/rodent cell hybrid panels identified TEF-1 on chromosome 11p15.2, between D11S1315 and D11S1334, extending a region of known synteny between human chromosomes 11 and 12 and arguing for an ancient divergence between these two closely related genes. Northern blot analysis revealed a striking similarity in the tissue distribution of RTEF-1 and TEF-1 mRNAs; skeletal muscle showed the highest abundance of both mRNAs, with lower levels detected in pancreas, placenta, and heart. Phylogenetic analysis of all known TEF-1-related proteins identified human RTEF-1 as one of four vertebrate members of this multigene family and further suggests that these genes diverged in the earliest metazoan ancestors.

  2. Identification of transcripts regulated by CUG-BP, Elav-like family member 1 (CELF1 in primary embryonic cardiomyocytes by RNA-seq

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    Yotam Blech-Hermoni

    2015-12-01

    Full Text Available CUG-BP, Elav-like family member 1 (CELF1 is a multi-functional RNA binding protein that regulates pre-mRNA alternative splicing in the nucleus, as well as polyadenylation status, mRNA stability, and translation in the cytoplasm [1]. Dysregulation of CELF1 has been implicated in cardiomyopathies in myotonic dystrophy type 1 and diabetes [2–5], but the targets of CELF1 regulation in the heart have not been systematically investigated. We previously demonstrated that in the developing heart CELF1 expression is restricted to the myocardium and peaks during embryogenesis [6–8]. To identify transcripts regulated by CELF1 in the embryonic myocardium, RNA-seq was used to compare the transcriptome of primary embryonic cardiomyocytes following siRNA-mediated knockdown of CELF1 to that of controls. Raw data files of the RNA-seq reads have been deposited in NCBI's Gene Expression Omnibus [9] under the GEO Series accession number GSE67360. These data can be used to identify transcripts whose levels or alternative processing (i.e., alternative splicing or polyadenylation site usage are regulated by CELF1, and should provide insight into the pathways and processes modulated by this important RNA binding protein during normal heart development and during cardiac pathogenesis.

  3. p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23 is controlled via a CHR promoter element bound by DREAM and MMB complexes.

    Directory of Open Access Journals (Sweden)

    Martin Fischer

    Full Text Available The microtubule-dependent molecular motor KIF23 (Kinesin family member 23 is one of two components of the centralspindlin complex assembled during late stages of mitosis. Formation of this complex is known as an essential step for cytokinesis. Here, we identified KIF23 as a new transcriptional target gene of the tumor suppressor protein p53. We showed that p53 reduces expression of KIF23 on the mRNA as well as the protein level in different cell types. Promoter reporter assays revealed that this repression results from downregulation of KIF23 promoter activity. CDK inhibitor p21(WAF1/CIP1 was shown to be necessary to mediate p53-dependent repression. Furthermore, we identified the highly conserved cell cycle genes homology region (CHR in the KIF23 promoter to be strictly required for p53-dependent repression as well as for cell cycle-dependent expression of KIF23. Cell cycle- and p53-dependent regulation of KIF23 appeared to be controlled by differential binding of DREAM and MMB complexes to the CHR element. With this study, we describe a new mechanism for transcriptional regulation of KIF23. Considering the strongly supporting function of KIF23 in cytokinesis, its p53-dependent repression may contribute to the prevention of uncontrolled cell growth.

  4. p53 and cell cycle dependent transcription of kinesin family member 23 (KIF23) is controlled via a CHR promoter element bound by DREAM and MMB complexes.

    Science.gov (United States)

    Fischer, Martin; Grundke, Inga; Sohr, Sindy; Quaas, Marianne; Hoffmann, Saskia; Knörck, Arne; Gumhold, Catalina; Rother, Karen

    2013-01-01

    The microtubule-dependent molecular motor KIF23 (Kinesin family member 23) is one of two components of the centralspindlin complex assembled during late stages of mitosis. Formation of this complex is known as an essential step for cytokinesis. Here, we identified KIF23 as a new transcriptional target gene of the tumor suppressor protein p53. We showed that p53 reduces expression of KIF23 on the mRNA as well as the protein level in different cell types. Promoter reporter assays revealed that this repression results from downregulation of KIF23 promoter activity. CDK inhibitor p21(WAF1/CIP1) was shown to be necessary to mediate p53-dependent repression. Furthermore, we identified the highly conserved cell cycle genes homology region (CHR) in the KIF23 promoter to be strictly required for p53-dependent repression as well as for cell cycle-dependent expression of KIF23. Cell cycle- and p53-dependent regulation of KIF23 appeared to be controlled by differential binding of DREAM and MMB complexes to the CHR element. With this study, we describe a new mechanism for transcriptional regulation of KIF23. Considering the strongly supporting function of KIF23 in cytokinesis, its p53-dependent repression may contribute to the prevention of uncontrolled cell growth.

  5. Switching antibiotics production on and off in actinomycetes by an IclR family transcriptional regulator from Streptomyces peucetius ATCC 27952.

    Science.gov (United States)

    Chaudhary, Amit Kumar; Singh, Bijay; Maharjan, Sushila; Jha, Amit Kumar; Kim, Byung-Gee; Sohng, Jae Kyung

    2014-08-01

    Doxorubicin, produced by Streptomyces peucetius ATCC 27952, is tightly regulated by dnrO, dnrN, and dnrI regulators. Genome mining of S. peucetius revealed the presence of the IclR (doxR) type family of transcription regulator mediating the signal-dependent expression of operons at the nonribosomal peptide synthetase gene cluster. Overexpression of doxR in native strain strongly repressed the drug production. Furthermore, it also had a negative effect on the regulatory system of doxorubicin, wherein the transcript of dnrI was reduced to the maximum level in comparision with the other two. Interestingly, the overexpression of the same gene also had strong inhibitory effects on the production of actinorhodin (blue pigment) and undecylprodigiosin (red pigment) in Streptomyces coelicolor M145, herboxidiene production in Streptomyces chromofuscus ATCC 49982, and spinosyn production in Saccharopolyspora spinosa NRRL 18395, respectively. Moreover, DoxR exhibited pleiotropic effects on the production of blue and red pigments in S. coelicolor when grown in different agar media, wherein the production of blue pigment was inhibited in R2YE medium and the red pigment was inhibited in YEME medium. However, the production of both blue and red pigments from S. coelicolor harboring doxR was halted in ISP2 medium, whereas S. coelicolor produced both pigmented antibiotics in the same plate. These consequences demonstrate that the on and off production of these antibiotics was not due to salt stress or media compositions, but was selectively controlled in actinomycetes.

  6. A Bioinformatics Analysis Reveals a Group of MocR Bacterial Transcriptional Regulators Linked to a Family of Genes Coding for Membrane Proteins

    Science.gov (United States)

    Milano, Teresa

    2016-01-01

    The MocR bacterial transcriptional regulators are characterized by an N-terminal domain, 60 residues long on average, possessing the winged-helix-turn-helix (wHTH) architecture responsible for DNA recognition and binding, linked to a large C-terminal domain (350 residues on average) that is homologous to fold type-I pyridoxal 5′-phosphate (PLP) dependent enzymes like aspartate aminotransferase (AAT). These regulators are involved in the expression of genes taking part in several metabolic pathways directly or indirectly connected to PLP chemistry, many of which are still uncharacterized. A bioinformatics analysis is here reported that studied the features of a distinct group of MocR regulators predicted to be functionally linked to a family of homologous genes coding for integral membrane proteins of unknown function. This group occurs mainly in the Actinobacteria and Gammaproteobacteria phyla. An analysis of the multiple sequence alignments of their wHTH and AAT domains suggested the presence of specificity-determining positions (SDPs). Mapping of SDPs onto a homology model of the AAT domain hinted at possible structural/functional roles in effector recognition. Likewise, SDPs in wHTH domain suggested the basis of specificity of Transcription Factor Binding Site recognition. The results reported represent a framework for rational design of experiments and for bioinformatics analysis of other MocR subgroups. PMID:27446613

  7. Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors.

    Science.gov (United States)

    Tuckfield, Annabel; Clouston, David R; Wilanowski, Tomasz M; Zhao, Lin-Lin; Cunningham, John M; Jane, Stephen M

    2002-03-01

    The Polycomb group (PcG) of proteins represses homeotic gene expression through the assembly of multiprotein complexes on key regulatory elements. The mechanisms mediating complex assembly have remained enigmatic since most PcG proteins fail to bind DNA. We now demonstrate that the human PcG protein dinG interacts with CP2, a mammalian member of the grainyhead-like family of transcription factors, in vitro and in vivo. The functional consequence of this interaction is repression of CP2-dependent transcription. The CP2-dinG interaction is conserved in evolution with the Drosophila factor grainyhead binding to dring, the fly homologue of dinG. Electrophoretic mobility shift assays demonstrate that the grh-dring complex forms on regulatory elements of genes whose expression is repressed by grh but not on elements where grh plays an activator role. These observations reveal a novel mechanism by which PcG proteins may be anchored to specific regulatory elements in developmental genes.

  8. Growth Rate of and Gene Expression in Bradyrhizobium diazoefficiens USDA110 due to a Mutation in blr7984, a TetR Family Transcriptional Regulator Gene.

    Science.gov (United States)

    Ohkama-Ohtsu, Naoko; Honma, Haruna; Nakagome, Mariko; Nagata, Maki; Yamaya-Ito, Hiroko; Sano, Yoshiaki; Hiraoka, Norina; Ikemi, Takaaki; Suzuki, Akihiro; Okazaki, Shin; Minamisawa, Kiwamu; Yokoyama, Tadashi

    2016-09-29

    Previous transcriptome analyses have suggested that a gene cluster including a transcriptional regulator (blr7984) of the tetracycline repressor family was markedly down-regulated in symbiosis. Since blr7984 is annotated to be the transcriptional repressor, we hypothesized that it is involved in the repression of genes in the genomic cluster including blr7984 in symbiotic bacteroids. In order to examine the function and involvement of the blr7984 gene in differentiation into bacteroids, we compared the free-living growth/symbiotic phenotype and gene expression between a blr7984-knockout mutant and the wild-type strain of Bradyrhizobium diazoefficiens USDA110. The mutant transiently increased the cell growth rate under free-living conditions and nodule numbers over those with the wild-type strain USDA110. The expression of three genes adjacent to the disrupted blr7984 gene was strongly up-regulated in the mutant in free-living and symbiotic cells. The mutant also induced the expression of genes for glutathione S-transferase, cytochrome c oxidases, ABC transporters, PTS sugar transport systems, and flagella synthesis under free-living conditions. bll7983 encoding glutathione S-transferase was up-regulated the most by the blr7984 disruption. Since redox regulation by glutathione is known to be involved in cell division in prokaryotes and eukaryotes, the strong expression of glutathione S-transferase encoded by the bll7983 gene may have caused redox changes in mutant cells, which resulted in higher rates of cell division.

  9. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    OpenAIRE

    Mustapha Aouida; Marta Rubio-Texeira; Thevelein, Johan M.; Richard Poulin; Dindial Ramotar

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant e...

  10. Transcriptome-Based Analysis of Dof Family Transcription Factors and Their Responses to Abiotic Stress in Tea Plant (Camellia sinensis

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    Hui Li

    2016-01-01

    Full Text Available Tea plant (Camellia sinensis (L. O. Kuntze is affected by abiotic stress during its growth and development. DNA-binding with one finger (Dof transcription factors (TFs play important roles in abiotic stress tolerance of plants. In this study, a total of 29 putative Dof TFs were identified based on transcriptome of tea plant, and the conserved domains and common motifs of these CsDof TFs were predicted and analyzed. The 29 CsDof proteins were divided into 7 groups (A, B1, B2, C1, C2.1, C2.2, and D2, and the interaction networks of Dof proteins in C. sinensis were established according to the data in Arabidopsis. Gene expression was analyzed in “Yingshuang” and “Huangjinya” under four experimental stresses by qRT-PCR. CsDof genes were expressed differentially and related to different abiotic stress conditions. In total, our results might suggest that there is a potential relationship between CsDof factors and tea plant stress resistance.

  11. Genome-wide analysis and identification of stress-responsive genes of the NAM-ATAF1,2-CUC2 transcription factor family in apple.

    Science.gov (United States)

    Su, Hongyan; Zhang, Shizhong; Yuan, Xiaowei; Chen, Changtian; Wang, Xiao-Fei; Hao, Yu-Jin

    2013-10-01

    NAC (NAM, ATAF1,2, and CUC2) proteins constitute one of the largest families of plant-specific transcription factors. To date, little is known about the NAC genes in the apple (Malus domestica). In this study, a total of 180 NAC genes were identified in the apple genome and were phylogenetically clustered into six groups (I-VI) with the NAC genes from Arabidopsis and rice. The predicted apple NAC genes were distributed across all of 17 chromosomes at various densities. Additionally, the gene structure and motif compositions of the apple NAC genes were analyzed. Moreover, the expression of 29 selected apple NAC genes was analyzed in different tissues and under different abiotic stress conditions. All of the selected genes, with the exception of four genes, were expressed in at least one of the tissues tested, which indicates that the NAC genes are involved in various aspects of the physiological and developmental processes of the apple. Encouragingly, 17 of the selected genes were found to respond to one or more of the abiotic stress treatments, and these 17 genes included not only the expected 7 genes that were clustered with the well-known stress-related marker genes in group IV but also 10 genes located in other subgroups, none of which contains members that have been reported to be stress-related. To the best of our knowledge, this report describes the first genome-wide analysis of the apple NAC gene family, and the results should provide valuable information for understanding the classification and putative functions of this family.

  12. Involvement of FOXO transcription factors, TRAIL-FasL/Fas, and sirtuin proteins family in canine coronavirus type II-induced apoptosis.

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    Gabriella Marfè

    Full Text Available n our previous study, we have shown that canine coronavirus type II (CCoV-II activates both extrinsic and intrinsic apoptotic pathway in a canine fibrosarcoma cell line (A-72 cells. Herein we investigated the role of Sirtuin and Forkhead box O (FOXO families in this experimental model using Nortern Blot and Western Blot analysis. Our results demonstrated that mitochondrial SIRT3 and SIRT4 protein expression increased from 12 and 24 h post infection (p.i. onwards, respectively, whereas the nuclear SIRT1 expression increased during the first 12 h p.i. followed by a decrease after 36 h p.i., reaching the same level of control at 48 h p.i. Sirtuins interact with/and regulate the activity of FOXO family proteins, and we herein observed that FOXO3A and FOXO1 expression increased significantly and stably from 12 h p.i. onwards. In addition, CCoV-II induces a remarkable increase in the expression of TNF-related apoptosis-inducing ligand (TRAIL, while we observed a slight up-regulation of FasL/Fas at 36 p.i. with a decrease of both proteins at the end of infection. Furthermore, we found that virus infection increased both bax translocation into mitochondria and decreased bcl-2 expression in cytosol in a time-dependent manner.These data suggest that FOXO transcription factors mediate pro-apoptotic effects of CCoV-II, in part due to activation of extrinsic apoptosis pathway, while some Sirtuin family members (such as SIRT3 and SIRT4 may be involved in intrinsic apoptotic pathway. Moreover, these results propose that TRAIL is an important mediator of cell death induced by CCoV-II during in vitro infection.

  13. Agp2, a Member of the Yeast Amino Acid Permease Family, Positively Regulates Polyamine Transport at the Transcriptional Level

    KAUST Repository

    Aouida, Mustapha

    2013-06-03

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3? nor sam3? single mutant is defective in polyamine transport, while the dur3? sam3? double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2? mutant. Studies of Agp2 localization indicate that in the double mutant dur3? sam3?, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport. © 2013 Aouida et al.

  14. Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

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    Mustapha Aouida

    Full Text Available Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant. Studies of Agp2 localization indicate that in the double mutant dur3Δ sam3Δ, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport.

  15. Agp2, a member of the yeast amino acid permease family, positively regulates polyamine transport at the transcriptional level.

    Science.gov (United States)

    Aouida, Mustapha; Rubio-Texeira, Marta; Rubio Texeira, Marta; Thevelein, Johan M; Poulin, Richard; Ramotar, Dindial

    2013-01-01

    Agp2 is a plasma membrane protein of the Saccharomyces cerevisiae amino acid transporter family, involved in high-affinity uptake of various substrates including L-carnitine and polyamines. The discovery of two high affinity polyamine permeases, Dur3 and Sam3, prompted us to investigate whether Agp2 directly transports polyamines or acts instead as a regulator. Herein, we show that neither dur3Δ nor sam3Δ single mutant is defective in polyamine transport, while the dur3Δ sam3Δ double mutant exhibits a sharp decrease in polyamine uptake and an increased resistance to polyamine toxicity similar to the agp2Δ mutant. Studies of Agp2 localization indicate that in the double mutant dur3Δ sam3Δ, Agp2-GFP remains plasma membrane-localized, even though transport of polyamines is strongly reduced. We further demonstrate that Agp2 controls the expression of several transporter genes including DUR3 and SAM3, the carnitine transporter HNM1 and several hexose, nucleoside and vitamin permease genes, in addition to SKY1 encoding a SR kinase that positively regulates low-affinity polyamine uptake. Furthermore, gene expression analysis clearly suggests that Agp2 is a strong positive regulator of additional biological processes. Collectively, our data suggest that Agp2 might respond to environmental cues and thus regulate the expression of several genes including those involved in polyamine transport.

  16. Purification, crystallization and preliminary X-ray crystallographic analysis of ST1022, a putative member of the Lrp/AsnC family of transcriptional regulators isolated from Sulfolobus tokodaii strain 7

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Noboru; Kumarevel, Thirumananseri, E-mail: tskvel@spring8.or.jp; Matsunaga, Emiko; Shinkai, Akeo [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Kuramitsu, Seiki [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Department of Biological Sciences, Graduate School of Science, Osaka University, Tayonaka, Osaka 560-0043 (Japan); Yokoyama, Shigeyuki, E-mail: tskvel@spring8.or.jp [RIKEN SPring-8 Center, Harima Institute, 1-1-1 Kouto, Sayo, Hyogo 679-5148 (Japan); Genomic Sciences Center, Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045 (Japan); Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2007-11-01

    A putative member of the Lrp/AsnC family of transcriptional regulators, ST1022 from S. tokodaii strain 7, has been purified and crystallized in the absence and presence of the effector l-glutamine. A molecular-replacement solution was found using the FL11 transcriptional regulator from Pyrococcus sp. OT3 as a model and structural refinement is under way. The Lrp/AsnC family of transcriptional regulators, also known as feast/famine transcriptional regulators, are widely distributed among bacteria and archaea. This family of proteins are likely to be involved in cellular metabolism, with exogenous amino acids functioning as effectors. Here, the crystallization and preliminary X-ray diffraction analysis of ST1022, a member of the Lrp/AsnC family of proteins, is reported with and without exogenous glutamine as the effector molecule. The crystals of native ST1022 and of the putative complex belong to the tetragonal space group I422, with unit-cell parameters a = b = 103.771, c = 73.297 Å and a = b = 103.846, c = 73.992 Å, respectively. Preliminary X-ray diffraction data analysis and molecular-replacement solution revealed the presence of one monomer per asymmetric unit.

  17. Angiotensin II-induced protein kinase D activates the ATF/CREB family of transcription factors and promotes StAR mRNA expression.

    Science.gov (United States)

    Olala, Lawrence O; Choudhary, Vivek; Johnson, Maribeth H; Bollag, Wendy B

    2014-07-01

    Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD may be mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

  18. The TEAD family transcription factor Scalloped regulates blood progenitor maintenance and proliferation in Drosophila through PDGF/VEGFR receptor (Pvr) signaling.

    Science.gov (United States)

    Ferguson, Gabriel B; Martinez-Agosto, Julian A

    2017-05-01

    The Drosophila lymph gland is a well-characterized hematopoietic organ in which a population of multipotent stem-like progenitors is maintained by a combination of signals from different cellular populations within the organ. The lymph gland serves as an ideal model both for the interrogation of signaling mechanisms involved in progenitor maintenance as well as a tool for the identification of novel regulatory mechanisms in the highly conserved process of hematopoiesis. Here, we demonstrate a requirement for the TEAD transcription factor Scalloped in the maintenance and proliferation of hematopoietic progenitors. We have characterized a novel population of hemocytes in the early lymph gland identified by the expression of Hand, Scalloped, and the PVR ligand PVF2. In this unique population, we show that Scalloped maintains PVF2 expression, which is required for hemocyte proliferation and achievement of normal lymph gland size. We further demonstrate that STAT signaling marks actively proliferating hemocytes in the early lymph gland, and inhibition of this pathway causes decreased lymph gland growth similar to loss of Scalloped and PVF2, demonstrating a requirement for PVR/STAT signaling in the regulation of lymph gland size. Finally, we demonstrate that Scalloped regulates PVR expression and the maintenance of progenitors downstream of PVR/STAT/ADGF signaling. These findings further establish the role of the TEAD family transcription factors in the regulation of important signaling molecules, and expand our mechanistic insight into the balance between progenitor maintenance and proliferation required for the regulation of lymph gland homeostasis. Copyright © 2017. Published by Elsevier Inc.

  19. Zebrafish brd2a and brd2b are paralogous members of the bromodomain-ET (BET family of transcriptional coregulators that show structural and expression divergence

    Directory of Open Access Journals (Sweden)

    Bee Katharine J

    2008-04-01

    Full Text Available Abstract Background Brd2 belongs to the bromodomain-extraterminal domain (BET family of transcriptional co-regulators, and functions as a pivotal histone-directed recruitment scaffold in chromatin modification complexes affecting signal-dependent transcription. Brd2 facilitates expression of genes promoting proliferation and is implicated in apoptosis and in egg maturation and meiotic competence in mammals; it is also a susceptibility gene for juvenile myoclonic epilepsy (JME in humans. The brd2 ortholog in Drosophila is a maternal effect, embryonic lethal gene that regulates several homeotic loci, including Ultrabithorax. Despite its importance, there are few systematic studies of Brd2 developmental expression in any organism. To help elucidate both conserved and novel gene functions, we cloned and characterized expression of brd2 cDNAs in zebrafish, a vertebrate system useful for genetic analysis of development and disease, and for study of the evolution of gene families and functional diversity in chordates. Results We identify cDNAs representing two paralogous brd2 loci in zebrafish, brd2a on chromosome 19 and brd2b on chromosome 16. By sequence similarity, syntenic and phylogenetic analyses, we present evidence for structural divergence of brd2 after gene duplication in fishes. brd2 paralogs show potential for modular domain combinations, and exhibit distinct RNA expression patterns throughout development. RNA in situ hybridizations in oocytes and embryos implicate brd2a and brd2b as maternal effect genes involved in egg polarity and egg to embryo transition, and as zygotic genes important for development of the vertebrate nervous system and for morphogenesis and differentiation of the digestive tract. Patterns of brd2 developmental expression in zebrafish are consistent with its proposed role in Homeobox gene regulation. Conclusion Expression profiles of zebrafish brd2 paralogs support a role in vertebrate developmental patterning and

  20. Functional expression of SAV3818, a putative TetR-family transcriptional regulatory gene from Streptomyces avermitilis, stimulates antibiotic production in Streptomyces species.

    Science.gov (United States)

    Duong, Cac Thi Phung; Lee, Han-Na; Choi, Si-Sun; Lee, Sang Yup; Kim, Eung-Soo

    2009-02-01

    Avermectin and its analogs are major commercial antiparasitic agents in the fields of animal health, agriculture, and human infections. Previously, comparative transcriptome analysis between the low-producer S. avermitilis ATCC31267 and the high-producer S. avermitilis ATCC31780 using a S. avermitilis whole genome chip revealed that 50 genes were overexpressed at least two-fold higher in S. avermitilis ATCC31780. To verify the biological significance of some of the transcriptomics-guided targets, five putative regulatory genes were individually cloned under the strong-andconstitutive promoter of the Streptomyces expression vector pSE34, followed by the transformation into the lowproducer S. avermitilis ATCC31267. Among the putative genes tested, three regulatory genes including SAV213, SAV3818, and SAV4023 exhibited stimulatory effects on avermectin production in S. avermitilis ATCC31267. Moreover, overexpression of SAV3818 also stimulated actinorhodin production in both S. coelicolor M145 and S. lividans TK21, implying that the SAV3818, a putative TetR-family transcriptional regulator, could be a global upregulator acting in antibiotic production in Streptomyces species.

  1. Roles of a novel Crp/Fnr family transcription factor Lmo0753 in soil survival, biofilm production and surface attachment to fresh produce of Listeria monocytogenes.

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    Joelle K Salazar

    Full Text Available Listeria monocytogenes is a foodborne bacterial pathogen and the causative agent of an infectious disease, listeriosis. L. monocytogenes is ubiquitous in nature and has the ability to persist in food processing environments for extended periods of time by forming biofilms and resisting industrial sanitization. Human listeriosis outbreaks are commonly linked to contaminated dairy products, ready-to-eat meats, and in recent years, fresh produce such as lettuce and cantaloupes. We identified a putative Crp/Fnr family transcription factor Lmo0753 that is highly specific to human-associated genetic lineages of L. monocytogenes. Lmo0753 possesses two conserved functional domains similar to the major virulence regulator PrfA in L. monocytogenes. To determine if Lmo0753 is involved in environmental persistence-related mechanisms, we compared lmo0753 deletion mutants with respective wild type and complementation mutants of two fully sequenced L. monocytogenes genetic lineage II strains 10403S and EGDe for the relative ability of growth under different nutrient availability and temperatures, soil survival, biofilm productivity and attachment to select fresh produce surfaces including romaine lettuce leaves and cantaloupe rinds. Our results collectively suggested that Lmo0753 plays an important role in L. monocytogenes biofilm production and attachment to fresh produce, which may contribute to the environmental persistence and recent emergence of this pathogen in human listeriosis outbreaks linked to fresh produce.

  2. Transcriptional profiling of the PDR gene family in rice roots in response to plant growth regulators, redox perturbations and weak organic acid stresses.

    Science.gov (United States)

    Moons, Ann

    2008-12-01

    The role of plant pleiotropic drug resistance (PDR) type ATP-binding cassette (ABC) transporters remains poorly understood. We characterized the expression of the rice pleiotropic drug resistance (PDR) gene family in roots, where PDR transporters are believed to have major functions. A prototypical oligonucleotide array was developed containing 70-mers chosen in the gene-specific 3' untranslated regions of the rice PDR genes, other full-molecule rice ABC transporter genes and relevant marker genes. Jasmonates, which are involved in plant defense and secondary metabolism, proved major inducers of PDR gene expression. Over half of the PDR genes were JA-induced in roots of rice; OsPDR9 to the highest level. Salicylic acid, involved in plant pathogen defense, markedly induced the expression of OsPDR20. OsPDR20 was cDNA cloned and characterized. Abscisic acid, typically involved in water deficit responses, particularly induced OsPDR3 in roots and shoot and OsPDR6 in rice leaves. OsPDR9 and OsPDR20 were furthermore up-regulated in response to dithiothreitol- or glutathione-induced redox perturbations. Exogenous application of the weak organic acids lactic acid, malic acid, and citric acid differentially induced the expression of OsPDR3, OsPDR8, OsPDR9 and OsPDR20 in rice seedling roots. This transcriptional survey represents a guide for the further functional analysis of individual PDR transporters in roots of rice.

  3. Genome-wide analysis of the WRKY transcription factor gene family in Gossypium raimondii and the expression of orthologs in cultivated tetraploid cotton

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    Caiping Cai

    2014-04-01

    Full Text Available WRKY proteins are members of a family of transcription factors in higher plants that function in plant responses to various physiological processes. We identified 120 candidate WRKY genes from Gossypium raimondii with corresponding expressed sequence tags in at least one of four cotton species, Gossypium hirsutum, Gossypium barbadense, Gossypium arboreum, and G. raimondii. These WRKY members were anchored on 13 chromosomes in G. raimondii with uneven distribution. Phylogenetic analysis showed that WRKY candidate genes can be classified into three groups, with 20 members in group I, 88 in group II, and 12 in group III. The 88 genes in group II were further classified into five subgroups, groups IIa–e, containing 7, 16, 37, 15, and 13 members, respectively. We characterized diversity in amino acid residues in the WRKY domain and/or other zinc finger motif regions in the WRKY proteins. The expression patterns of WRKY genes revealed their important roles in diverse functions in cotton developmental stages of vegetative and reproductive growth and stress response. Structural and expression analyses show that WRKY proteins are a class of important regulators of growth and development and play key roles in response to stresses in cotton.

  4. Genome-wide analysis of the WRKY transcription factor gene family in Gossypium raimondii and the expression of orthologs in cultivated tetraploid cotton

    Institute of Scientific and Technical Information of China (English)

    Caiping; Cai; Erli; Niu; Hao; Du; Liang; Zhao; Yue; Feng; Wangzhen; Guo

    2014-01-01

    WRKY proteins are members of a family of transcription factors in higher plants that function in plant responses to various physiological processes.We identified 120 candidate WRKY genes from Gossypium raimondii with corresponding expressed sequence tags in at least one of four cotton species,Gossypium hirsutum,Gossypium barbadense,Gossypium arboreum,and G.raimondii.These WRKY members were anchored on 13 chromosomes in G.raimondii with uneven distribution.Phylogenetic analysis showed that WRKY candidate genes can be classified into three groups,with 20 members in group I,88 in group II,and 12 in group III.The88 genes in group II were further classified into five subgroups,groups IIa–e,containing 7,16,37,15,and 13 members,respectively.We characterized diversity in amino acid residues in the WRKY domain and/or other zinc finger motif regions in the WRKY proteins.The expression patterns of WRKY genes revealed their important roles in diverse functions in cotton developmental stages of vegetative and reproductive growth and stress response.Structural and expression analyses show that WRKY proteins are a class of important regulators of growth and development and play key roles in response to stresses in cotton.

  5. Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability.

    Science.gov (United States)

    Schanze, Ina; Schanze, Denny; Bacino, Carlos A; Douzgou, Sofia; Kerr, Bronwyn; Zenker, Martin

    2013-02-01

    Intellectual disability (ID) is a clinically and genetically heterogeneous condition; the cause is unknown in most non-specific and sporadic cases. To establish an etiological basis in those patients represents a difficult challenge. Over the last years it has become apparent that chromosomal rearrangements below the detection level of conventional karyotyping contribute significantly to the cause of ID. We present three patients with non-specific intellectual disability who all have overlapping microdeletions in the chromosomal region 12p12.1. De novo occurrence of the deletion could be proven in the two cases from which parental samples were available. All three identified deletions have different breakpoints and range in size from 120 kb to 4.9 Mb. The smallest deletion helps to narrow down the critical region to a genomic segment (chr12:23,924,800-24,041,698, build 37/hg19) encompassing only one gene, SOX5. SOX5 is a member of the SOX (SRY-related HMG-box) family of transcription factors shown to play roles in chondroblast function, oligodendrocyte differentiation and migration, as well as ensuring proper development of specific neuronal cell types. Because of these biological functions, mutations in SOX5 are predicted to cause complex disease syndromes, as it is the case for other SOX genes, but such mutations have not yet been identified. Our findings indicate that haploinsufficiency of SOX5 is a cause of intellectual disability without any striking physical anomalies.

  6. Identification of immunity-related genes in prostate cancer and potential role of the ETS family of transcription factors in their regulation.

    Science.gov (United States)

    Shaikhibrahim, Zaki; Lindstrot, Andreas; Ellinger, Jörg; Rogenhofer, Sebastian; Buettner, Reinhard; Wernert, Nicolas

    2011-11-01

    The role of the immune response in tumor progression, and disease outcome is still debated, and a lack of knowledge of the immune defenses in prostate cancer still exists. In addition, the ETS family of transcription factors which is involved in translocations frequently found in prostate cancer is reported to be essential for the regulation of immunity-related genes. In order to identify immunity-related genes in prostate cancer, we performed two microarrays using RNA extracted from laser microdissected glands of the normal prostate proper (or the peripheral zone) and moderately and poorly differentiated prostate carcinomas from patients who had undergone radical prostatectomy. Many differentially expressed genes were found, however, only immunity-related genes (B cell, innate, and T cell immunity) with an expression of more than 10-fold increase or decrease and a Pimmunity-related genes in prostate cancer, and provided insights into their potential regulation, which may lead to a better early detection, immunotherapy, and therapeutic drug treatment of this disease. Unraveling the dynamics of the ETS-immunity-related genes will provide an invaluable insight into understanding prostate cancer immunology.

  7. The LacI–Family Transcription Factor, RbsR, Is a Pleiotropic Regulator of Motility, Virulence, Siderophore and Antibiotic Production, Gas Vesicle Morphogenesis and Flotation in Serratia

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    Chin M. Lee

    2017-09-01

    Full Text Available Gas vesicles (GVs are proteinaceous, gas-filled organelles used by some bacteria to enable upward movement into favorable air/liquid interfaces in aquatic environments. Serratia sp. ATCC39006 (S39006 was the first enterobacterium discovered to produce GVs naturally. The regulation of GV assembly in this host is complex and part of a wider regulatory network affecting various phenotypes, including antibiotic biosynthesis. To identify new regulators of GVs, a comprehensive mutant library containing 71,000 insertion mutants was generated by random transposon mutagenesis and 311 putative GV-defective mutants identified. Three of these mutants were found to have a transposon inserted in a LacI family transcription regulator gene (rbsR of the putative ribose operon. Each of these rbsR mutants was GV-defective; no GVs were visible by phase contrast microscopy (PCM or transmission electron microscopy (TEM. GV deficiency was caused by the reduction of gvpA1 and gvrA transcription (the first genes of the two contiguous operons in the GV gene locus. Our results also showed that a mutation in rbsR was highly pleiotropic; the production of two secondary metabolites (carbapenem and prodigiosin antibiotics was abolished. Interestingly, the intrinsic resistance to the carbapenem antibiotic was not affected by the rbsR mutation. In addition, the production of a siderophore, cellulase and plant virulence was reduced in the mutant, whereas it exhibited increased swimming and swarming motility. The RbsR protein was predicted to bind to regions upstream of at least 18 genes in S39006 including rbsD (the first gene of the ribose operon and gvrA. Electrophoretic mobility shift assays (EMSA confirmed that RbsR bound to DNA sequences upstream of rbsD, but not gvrA. The results of this study indicate that RbsR is a global regulator that affects the modulation of GV biogenesis, but also with complex pleiotropic physiological impacts in S39006.

  8. Dumpy-30 family members as determinants of male fertility and interaction partners of metal-responsive transcription factor 1 (MTF-1 in Drosophila

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    Renkawitz-Pohl Renate

    2008-06-01

    Full Text Available Abstract Background Metal-responsive transcription factor 1 (MTF-1, which binds to metal response elements (MREs, plays a central role in transition metal detoxification and homeostasis. A Drosophila interactome analysis revealed two candidate dMTF-1 interactors, both of which are related to the small regulatory protein Dumpy-30 (Dpy-30 of the worm C. elegans. Dpy-30 is the founding member of a protein family involved in chromatin modifications, notably histone methylation. Mutants affect mating type in yeast and male mating in C. elegans. Results Constitutive expression of the stronger interactor, Dpy-30L1 (CG6444, in transgenic flies inhibits MTF-1 activity and results in elevated sensitivity to Cd(II and Zn(II, an effect that could be rescued by co-overexpression of dMTF-1. Electrophoretic mobility shift assays (EMSA suggest that Dpy-30L1 interferes with the binding of MTF-1 to its cognate MRE binding site. Dpy-30L1 is expressed in the larval brain, gonads, imaginal discs, salivary glands and in the brain, testes, ovaries and salivary glands of adult flies. Expression of the second interactor, Dpy-30L2 (CG11591, is restricted to larval male gonads, and to the testes of adult males. Consistent with these findings, dpy-30-like transcripts are also prominently expressed in mouse testes. Targeted gene disruption by homologous recombination revealed that dpy-30L1 knockout flies are viable and show no overt disruption of metal homeostasis. In contrast, the knockout of the male-specific dpy-30L2 gene results in male sterility, as does the double knockout of dpy-30L1 and dpy-30L2. A closer inspection showed that Dpy-30L2 is expressed in elongated spermatids but not in early or mature sperm. Mutant sperm had impaired motility and failed to accumulate in sperm storage organs of females. Conclusion Our studies help to elucidate the physiological roles of the Dumpy-30 proteins, which are conserved from yeast to humans and typically act in concert with

  9. Gclust Server: 120137 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 120137 Mes_Meso_2630 Cluster Sequences Related Sequences(23) 386 transcriptional re...gulator, LysR family 1 1.00e-31 0.0 0.0 0.0 0.0 3.23 0.0 Show 120137 Cluster ID 120137 Sequence ID Mes_Meso_

  10. Gclust Server: 100159 [Gclust Server

    Lifescience Database Archive (English)

    Full Text Available 100159 Mtu_Rv0377 Cluster Sequences Related Sequences(171) 321 PROBABLE TRANSCRIPTI...ONAL REGULATORY PROTEIN (PROBABLY LYSR-FAMILY) 1 1.00e-99 0.0 0.0 0.0 0.0 3.23 0.0 Show 100159 Cluster ID 1001

  11. Coexpression Analysis Identifies Rice Starch Regulator1, a Rice AP2/EREBP Family Transcription Factor, as a Novel Rice Starch Biosynthesis Regulator1[W][OA

    Science.gov (United States)

    Fu, Fang-Fang; Xue, Hong-Wei

    2010-01-01

    Starch biosynthesis is important for plant development and is a critical factor in crop quality and nutrition. As a complex metabolic pathway, the regulation of starch biosynthesis is still poorly understood. We here present the identification of candidate regulators for starch biosynthesis by gene coexpression analysis in rice (Oryza sativa). Starch synthesis genes can be grouped into type I (in seeds; sink tissues) and type II (in vegetative tissues; source tissues), and 307 and 621 coexpressed genes are putatively involved in the regulation of starch biosynthesis in rice seeds and vegetative tissues, respectively. Among these genes, Rice Starch Regulator1 (RSR1), an APETALA2/ethylene-responsive element binding protein family transcription factor, was found to negatively regulate the expression of type I starch synthesis genes, and RSR1 deficiency results in the enhanced expression of starch synthesis genes in seeds. Seeds of the knockout mutant rsr1 consistently show the increased amylose content and altered fine structure of amylopectin and consequently form the round and loosely packed starch granules, resulting in decreased gelatinization temperature. In addition, rsr1 mutants have a larger seed size and increased seed mass and yield. In contrast, RSR1 overexpression suppresses the expression of starch synthesis genes, resulting in altered amylopectin structure and increased gelatinization temperature. Interestingly, a decreased proportion of A chains in rsr1 results in abnormal starch granules but reduced gelatinization temperature, whereas an increased proportion of A chains in RSR1-overexpressing plants leads to higher gelatinization temperatures, which is novel and different from previous reports, further indicating the complicated regulation of starch synthesis and determination of the physicochemical properties of starch. These results demonstrate the potential of coexpression analysis for studying rice starch biosynthesis and the regulation of a

  12. Human endogenous retrovirus family HERV-K(HML-2) RNA transcripts are selectively packaged into retroviral particles produced by the human germ cell tumor line Tera-1 and originate mainly from a provirus on chromosome 22q11.21.

    Science.gov (United States)

    Ruprecht, Klemens; Ferreira, Humberto; Flockerzi, Aline; Wahl, Silke; Sauter, Marlies; Mayer, Jens; Mueller-Lantzsch, Nikolaus

    2008-10-01

    The human germ cell tumor line Tera-1 produces retroviral particles which are encoded by the human endogenous retrovirus family HERV-K(HML-2). We show here, by quantitative reverse transcriptase PCR, that HML-2 gag and env RNA transcripts are selectively packaged into Tera-1 retroviral particles, whereas RNAs from cellular housekeeping genes and from other HERV families (HERV-H and HERV-W) are nonselectively copackaged. Assignment of cloned HML-2 gag and env cDNAs from Tera-1 retroviral particles to individual HML-2 loci in the human genome demonstrated that HML-2 RNA transcripts packaged into Tera-1 retroviral particles originate almost exclusively from an HML-2 provirus on chromosome 22q11.21. Based on relative cloning frequencies, this provirus was the most active among a total of eight transcribed HML-2 loci identified in Tera-1 cells. These data suggest that at least one HML-2 element, that is, the HML-2 provirus on 22q11.21, has retained the capacity for packaging RNA into HML-2-encoded retroviral particles. Given its elevated transcriptional activity and the presence of a full-length Gag open reading frame, the 22q11.21 HML-2 provirus may also significantly contribute to Gag protein and thus particle production in Tera-1 cells. Our findings provide important clues to the generation and biological properties of HML-2-encoded particles. In addition, copackaging of non-HML-2 HERV transcripts in HML-2-encoded particles should inform the debate about endogenous retroviral particles putatively encoded by non-HML-2 HERV families that have previously been described for other human diseases, such as multiple sclerosis.

  13. GATA-4/-6 and HNF-1/-4 families of transcription factors control the transcriptional regulation of the murine Muc5ac mucin during stomach development and in epithelial cancer cells.

    Science.gov (United States)

    Jonckheere, Nicolas; Vincent, Audrey; Franquet-Ansart, Hélène; Witte-Bouma, Janneke; Korteland-van Male, Anita; Leteurtre, Emmanuelle; Renes, Ingrid B; Van Seuningen, Isabelle

    2012-08-01

    During human embryonic and fetal development of the gastrointestinal tract, the gene encoding the MUC5AC mucin has a spatio-temporal pattern of expression restricted to the stomach. In order to better understand the molecular mechanisms responsible for this restricted pattern of expression, we have studied Muc5ac expression in the developing stomach of the mouse and correlated it to that of transcription factors known to be involved in cell differentiation programs during development. Our results indicate that GATA-6 and HNF-4α expression increased concomitantly with the induction of Muc5ac expression in embryonic stomach. We then studied Muc5ac transcriptional regulation by these transcription factors and showed that they all transactivate Muc5ac promoter. We also identified several active GATA-4/-5/-6 and HNF-1/-4 cis-elements using gel shift assays, chromatin immunoprecipitation and site-directed mutagenesis. Among all Muc5ac regulators, only GATA-6 and HNF-4a expression was concomitant to that of Muc5ac in the developing stomach. This is thus in favor of an important role for these two transcription factors as regulators of expression of the Muc5ac mucin during stomach development and in epithelial cancer cells.

  14. Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2)

    OpenAIRE

    Bhukya, Hussain; Bhujbalrao, Ruchika; Bitra, Aruna; Anand, Ruchi

    2014-01-01

    Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class of transcription factors that are induced by γ-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 Å. Binding of the DNA resu...

  15. GntR family regulator SCO6256 is involved in antibiotic production and conditionally regulates the transcription of myo-inositol catabolic genes in Streptomyces coelicolor A3(2).

    Science.gov (United States)

    Yu, Lingjun; Gao, Wenyan; Li, Shuxian; Pan, Yuanyuan; Liu, Gang

    2016-03-01

    SCO6256 belongs to the GntR family and shows 74% identity with SCO6974, which is the repressor of myo-inositol catabolism in Streptomyces coelicolor A3(2). Disruption of SCO6256 significantly enhanced the transcription of myo-inositol catabolic genes in R2YE medium. The purified recombinant SCO6256 directly bound to the upstream regions of SCO2727, SCO6978 and SCO6985, as well as its encoding gene. Footprinting assays demonstrated that SCO6256 bound to the same sites in the myo-inositol catabolic gene cluster as SCO6974. The expression of SCO6256 was repressed by SCO6974 in minimal medium with myo-inositol as the carbon source, but not in R2YE medium. Glutathione-S-transferase pull-down assays demonstrated that SCO6974 and SCO6256 interacted with each other; and both of the proteins controlled the transcription of myo-inositol catabolic genes in R2YE medium. These results indicated SCO6256 regulates the transcription of myo-inositol catabolic genes in coordination with SCO6974 in R2YE medium. In addition, SCO6256 negatively regulated the production of actinorhodin and calcium-dependent antibiotic via control of the transcription of actII-ORF4 and cdaR. SCO6256 bound to the upstream region of cdaR and the binding sequence was proved to be TTTCGGCACGCAGACAT, which was further confirmed through base substitution. Four putative targets (SCO2652, SCO4034, SCO4237 and SCO6377) of SCO6256 were found by screening the genome sequence of Strep. coelicolor A3(2) based on the conserved binding motif, and confirmed by transcriptional analysis and electrophoretic mobility shift assays. These results revealed that SCO6256 is involved in the regulation of myo-inositol catabolic gene transcription and antibiotic production in Strep. coelicolor A3(2).

  16. Preaxial polydactyly/triphalangeal thumb is associated with changed transcription factor-binding affinity in a family with a novel point mutation in the long-range cis-regulatory element ZRS

    DEFF Research Database (Denmark)

    Farooq, Muhammad; Troelsen, Jesper T; Boyd, Mette

    2010-01-01

    have been reported in ZRS, the underlying regulatory mechanism is still unknown. In this study, we analyzed the effect on transcription factor binding of a novel ZRS point mutation (463T>G) in a Pakistani family with preaxial polydactyly and triphalangeal thumb. Electrophoretical mobility shift assay......A cis-regulatory sequence also known as zone of polarizing activity (ZPA) regulatory sequence (ZRS) located in intron 5 of LMBR1 is essential for expression of sonic hedgehog (SHH) in the developing posterior limb bud mesenchyme. Even though many point mutations causing preaxial duplication defects...

  17. Characterization of SAV7471, a TetR-family transcriptional regulator involved in the regulation of coenzyme A metabolism in Streptomyces avermitilis.

    Science.gov (United States)

    Liu, Yanping; Yan, Tingting; Jiang, Libin; Wen, Ying; Song, Yuan; Chen, Zhi; Li, Jilun

    2013-10-01

    The role of a tetR transcriptional regulatory gene (SAV7471) in avermectin production in the Gram-positive soil bacterium Streptomyces avermitilis was investigated by gene deletion, complementation, and overexpression experiments. Gene deletion of the SAV7471 open reading frame resulted in avermectin overproduction. The deletion also resulted in overexpression of SAV7472-SAV7473 transcripts, which encode a protein of unknown function and a flavoprotein possibly involved in pantothenate and coenzyme A (CoA) metabolism. EMSAs and footprinting assays showed that SAV7471 can bind to two palindromic sequences with high similarity in the intergenic region between SAV7471 and SAV7472, a region that contains the apparent transcription start sites for each gene detected by rapid amplification of 5' cDNA ends (5'-RACE). In addition to SAV7472-SAV7473, at least two genes (SAV1104 and SAV1258) involved in CoA metabolism are negatively controlled by SAV7471. By negatively regulating the transcription of the target genes SAV7472-SAV7473 and other genes involved in CoA metabolism, SAV7471 may affect cellular metabolic flux and may thereby indirectly regulate avermectin biosynthesis.

  18. The solution structure of DNA-free Pax-8 paired box domain accounts for redox regulation of transcriptional activity in the Pax protein family

    NARCIS (Netherlands)

    Codutti, L.; van Ingen, H.; Vascotto, C.; Fogolari, F.; Corazza, A.; Tell, G.; Quadrifoglio, F.; Viglino, P.; Boelens, R.; Esposito, G.

    2008-01-01

    Pax-8 is a transcription factor belonging to the PAX genes superfamily and its crucial role has been proven both in embryo and in the adult organism. Pax-8 activity is regulated via a redoxbased mechanism centered on the glutathionylation of specific cysteines in the N-terminal region (Cys45 and

  19. Evolution and diversification of the basal transcription machinery.

    Science.gov (United States)

    Duttke, Sascha H C

    2015-03-01

    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems.

  20. Disruption of mutually negative regulatory feedback loop between interferon-inducible p202 protein and the E2F family of transcription factors in lupus-prone mice

    Science.gov (United States)

    Panchanathan, Ravichandran; Xin, Hong; Choubey, Divaker

    2010-01-01

    Summary Studies have identified interferon-inducible Ifi202 gene as a lupus susceptibility gene (encoding p202 protein) in mouse models of lupus disease. However, signaling pathways that regulate the Ifi202 expression in cells remain to be elucidated. We found that steady-state levels of Ifi202 mRNA and protein were high in mouse embryonic fibroblasts (MEFs) from E2F1-knockout (E2F1-/-) and E2F1 and E2F2 double knockout (E2F1-/- E2F2-/-) mice than isogenic wild type MEFs. Moreover, overexpression of E2F1 in mouse fibroblasts decreased expression of p202. Furthermore, expression of E2F1, but not E2F4, transcription factor in mouse fibroblasts repressed the activity of 202-luc-reporter in promoter-reporter assays. Interestingly, the E2F1-mediated transcriptional repression of the 202-luc-reporter was independent of p53 and pRb expression. However, the repression was dependent on the ability of E2F1 to bind DNA. We have identified a potential E2F DNA-binding site in the 5′-regulatory region of the Ifi202 gene and mutations in this E2F DNA-binding site reduced the E2F1-mediated transcriptional repression of 202-luc-reporter. Because p202 inhibits the E2F1-mediated transcriptional activation of genes, we compared the expression of E2F1 and its target genes in splenic cells from lupus-prone B6.Nba2 congenic mice, which express increased levels of p202, with age-matched C57BL/6 mice. We found that increased expression of Ifi202 in the congenic mice was associated with inhibition of E2F1-mediated transcription and decreased expression of E2F1 and its target genes that encode pro-apoptotic proteins. Our observations support for the idea that increased Ifi202 expression in certain strain of mice contributes to lupus susceptibility in part by inhibiting E2F1-mediated functions. PMID:18424712

  1. Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare)WRKY transcription factor family reveals putatively retained functions betweenmonocots and dicots

    Energy Technology Data Exchange (ETDEWEB)

    Mangelsen, Elke; Kilian, Joachim; Berendzen, Kenneth W.; Kolukisaoglu, Uner; Harter, Klaus; Jansson, Christer; Wanke, Dierk

    2008-02-01

    WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare), three different WRKY proteins have been characterized so far, as regulators in sucrose signaling, in pathogen defense, and in response to cold and drought, respectively. However, their phylogenetic relationship remained unresolved. In this study, we used the available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY) genes. According to their structural features the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs. HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in mono- and dicot species.

  2. Phylogenetic and comparative gene expression analysis of barley (Hordeum vulgare WRKY transcription factor family reveals putatively retained functions between monocots and dicots

    Directory of Open Access Journals (Sweden)

    Jansson Christer

    2008-04-01

    Full Text Available Abstract Background WRKY proteins belong to the WRKY-GCM1 superfamily of zinc finger transcription factors that have been subject to a large plant-specific diversification. For the cereal crop barley (Hordeum vulgare, three different WRKY proteins have been characterized so far as regulators in sucrose signaling, pathogen defense, and in response to cold and drought. However, their phylogenetic relationship remained unresolved. Results In this study, we used available sequence information to identify a minimum number of 45 barley WRKY transcription factor (HvWRKY genes. According to their structural features, the HvWRKY factors were classified into the previously defined polyphyletic WRKY subgroups 1 to 3. Furthermore, we could assign putative orthologs of the HvWRKY proteins in Arabidopsis and rice. While in most cases clades of orthologous proteins were formed within each group or subgroup, other clades were composed of paralogous proteins for the grasses and Arabidopsis only, which is indicative of specific gene radiation events. To gain insight into their putative functions, we examined expression profiles of WRKY genes from publicly available microarray data resources and found group specific expression patterns. While putative orthologs of the HvWRKY transcription factors have been inferred from phylogenetic sequence analysis, we performed a comparative expression analysis of WRKY genes in Arabidopsis and barley. Indeed, highly correlative expression profiles were found between some of the putative orthologs. Conclusion HvWRKY genes have not only undergone radiation in monocot or dicot species, but exhibit evolutionary traits specific to grasses. HvWRKY proteins exhibited not only sequence similarities between orthologs with Arabidopsis, but also relatedness in their expression patterns. This correlative expression is indicative for a putative conserved function of related WRKY proteins in monocot and dicot species.

  3. Quantitative RT-PCR based platform for rapid quantification of the transcripts of highly homologous multigene families and their members during grain development

    DEFF Research Database (Denmark)

    Kaczmarczyk, Agnieszka Ewa; Bowra, Steve; Elek, Zoltan;

    2012-01-01

    Background Cereal storage proteins represent one of the most important sources of protein for food and feed and they are coded by multigene families. The expression of the storage protein genes exhibits a temporal fluctuation but also a response to environmental stimuli. Analysis of temporal gene...

  4. Yas3p, an Opi1 Family Transcription Factor, Regulates Cytochrome P450 Expression in Response to n-Alkanes in Yarrowia lipolytica*

    OpenAIRE

    Hirakawa, Kiyoshi; Kobayashi, Satoshi; Inoue, Takuro; Endoh-Yamagami, Setsu; Fukuda, Ryouichi; Ohta, Akinori

    2009-01-01

    In the alkane-assimilating yeast Yarrowia lipolytica, the expression of ALK1, a gene encoding cytochrome P450 that catalyzes the first step of n-alkane oxidation, is induced by n-alkanes. We previously demonstrated that two basic helix-loop-helix proteins, Yas1p and Yas2p, activate the transcription of ALK1 in an alkane-dependent manner by forming a heterocomplex and binding to alkane-responsive element 1 (ARE1), a cis-acting element in the ALK1 promoter. Here we i...

  5. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...

  6. Nucleocytoplasmic shuttling of transcription factors

    DEFF Research Database (Denmark)

    Cartwright, P; Helin, K

    2000-01-01

    To elicit the transcriptional response following intra- or extracellular stimuli, the signals need to be transmitted to their site of action within the nucleus. The nucleocytoplasmic shuttling of transcription factors is a mechanism mediating this process. The activation and inactivation...... transcription factor families are regulated by similar mechanisms, there are several differences that allow for the specific activation of each transcription factor. This review discusses the general import and export pathways found to be common amongst many different transcription factors, and highlights...... of the transcriptional response is essential for cells to progress through the cell cycle in a normal manner. The involvement of cytoplasmic and nuclear accessory molecules, and the general nuclear membrane transport components, are essential for this process. Although nuclear import and export for different...

  7. Structural and functional basis of transcriptional regulation by TetR family protein CprB from S. coelicolor A3(2).

    Science.gov (United States)

    Bhukya, Hussain; Bhujbalrao, Ruchika; Bitra, Aruna; Anand, Ruchi

    2014-09-01

    Antibiotic production and resistance pathways in Streptomyces are dictated by the interplay of transcriptional regulatory proteins that trigger downstream responses via binding to small diffusible molecules. To decipher the mode of DNA binding and the associated allosteric mechanism in the sub-class of transcription factors that are induced by γ-butyrolactones, we present the crystal structure of CprB in complex with the consensus DNA element to a resolution of 3.25 Å. Binding of the DNA results in the restructuring of the dimeric interface of CprB, inducing a pendulum-like motion of the helix-turn-helix motif that inserts into the major groove. The crystal structure revealed that, CprB is bound to DNA as a dimer of dimers with the mode of binding being analogous to the broad spectrum multidrug transporter protein QacR from the antibiotic resistant strain Staphylococcus aureus. It was demonstrated that the CprB displays a cooperative mode of DNA binding, following a clamp and click model. Experiments performed on a subset of DNA sequences from Streptomyces coelicolor A3(2) suggest that CprB is most likely a pleiotropic regulator. Apart from serving as an autoregulator, it is potentially a part of a network of proteins that modulates the γ-butyrolactone synthesis and antibiotic regulation pathways in S. coelicolor A3(2).

  8. Transcription factories

    Science.gov (United States)

    Rieder, Dietmar; Trajanoski, Zlatko; McNally, James G.

    2012-01-01

    There is considerable evidence that transcription does not occur homogeneously or diffusely throughout the nucleus, but rather at a number of specialized, discrete sites termed transcription factories. The factories are composed of ~4–30 RNA polymerase molecules, and are associated with many other molecules involved in transcriptional activation and mRNA processing. Some data suggest that the polymerase molecules within a factory remain stationary relative to the transcribed DNA, which is thought to be reeled through the factory site. There is also some evidence that transcription factories could help organize chromatin and nuclear structure, contributing to both the formation of chromatin loops and the clustering of active and co-regulated genes. PMID:23109938

  9. The crystal structures of apo and cAMP-bound GlxR from Corynebacterium glutamicum reveal structural and dynamic changes upon cAMP binding in CRP/FNR family transcription factors.

    Directory of Open Access Journals (Sweden)

    Philip D Townsend

    Full Text Available The cyclic AMP-dependent transcriptional regulator GlxR from Corynebacterium glutamicum is a member of the super-family of CRP/FNR (cyclic AMP receptor protein/fumarate and nitrate reduction regulator transcriptional regulators that play central roles in bacterial metabolic regulatory networks. In C. glutamicum, which is widely used for the industrial production of amino acids and serves as a non-pathogenic model organism for members of the Corynebacteriales including Mycobacterium tuberculosis, the GlxR homodimer controls the transcription of a large number of genes involved in carbon metabolism. GlxR therefore represents a key target for understanding the regulation and coordination of C. glutamicum metabolism. Here we investigate cylic AMP and DNA binding of GlxR from C. glutamicum and describe the crystal structures of apo GlxR determined at a resolution of 2.5 Å, and two crystal forms of holo GlxR at resolutions of 2.38 and 1.82 Å, respectively. The detailed structural analysis and comparison of GlxR with CRP reveals that the protein undergoes a distinctive conformational change upon cyclic AMP binding leading to a dimer structure more compatible to DNA-binding. As the two binding sites in the GlxR homodimer are structurally identical dynamic changes upon binding of the first ligand are responsible for the allosteric behavior. The results presented here show how dynamic and structural changes in GlxR lead to optimization of orientation and distance of its two DNA-binding helices for optimal DNA recognition.

  10. Characterization of the fatty acyl elongase (elovl) gene family, and hepatic elovl and delta-6 fatty acyl desaturase transcript expression and fatty acid responses to diets containing camelina oil in Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Xue, Xi; Feng, Charles Y; Hixson, Stefanie M; Johnstone, Kim; Anderson, Derek M; Parrish, Christopher C; Rise, Matthew L

    2014-09-01

    For aquaculture to become sustainable, there is a need to substitute fish oil [FO, rich in ω3 long chain polyunsaturated fatty acids (LC-PUFA) such as 20:5ω3 (EPA) and 22:6ω3 (DHA)] in aquafeed with plant oils such as camelina oil [CO, rich in C18 PUFA such as 18:3ω3 (ALA) and 18:2ω6 (LNA)]. The LC-PUFA are essential components in fish diets for maintaining optimal health, physiology and growth. However, most marine fish including Atlantic cod are inefficient at producing LC-PUFA from shorter chain precursors. Since elovl genes encode enzymes that play key roles in fatty acid biosynthesis, we hypothesized that they may be involved in Atlantic cod responses to diets rich in 18:3ω3 and 18:2ω6. Ten members of the cod elovl gene family were characterized at the mRNA level. RT-PCR was used to study constitutive expression of elovl transcripts in fifteen tissues. Some transcripts (e.g. elovl5) were ubiquitously expressed, while others had tissue-specific expression (e.g. elovl4a in brain and eye). Cod fed a CO-containing diet (100% CO replacement of FO and including solvent-extracted fish meal) had significantly lower weight gain, with significant up-regulation of elovl5 and fadsd6 transcripts in the liver as shown by QPCR analysis, compared with cod on a FO control diet after a 13-week trial. Multivariate statistical analyses (SIMPER and PCA) indicated that high 18:3ω3 and/or low ω3 LC-PUFA levels in the liver were associated with the up-regulation of elovl5 and fadsd6, which are involved in LC-PUFA biosynthesis in cod.

  11. The MarR family transcription factor Rv1404 coordinates adaptation of Mycobacterium tuberculosis to acid stress via controlled expression of Rv1405c, a virulence-associated methyltransferase.

    Science.gov (United States)

    Healy, Claire; Golby, Paul; MacHugh, David E; Gordon, Stephen V

    2016-03-01

    Coordinated regulation of gene expression is essential for pathogen adaptation in vivo. Understanding the control of these virulence circuits in the TB pathogen Mycobacterium tuberculosis is a key challenge if we are to increase our basic understanding of how this organism establishes infection. In this study we focused on the transcriptional regulator Rv1404 that shows similarity to the MarR family of transcriptional repressors. Rv1404 derepresses a set of genes in vivo that have been implicated in virulence and may therefore allow adaptation of M. tuberculosis to the intracellular environment. We used a combination of ChIP-qPCR and Electromobility Band Shift Assays (EMSA) to show that Rv1404 coordinates gene expression in response to stresses such as low pH in M. tuberculosis. Two genes regulated by Rv1404, rv1403c and rv1405c, encode putative SAM-dependent methyltransferases. To elucidate gene function, M. tuberculosis rv1403c and rv1405c mutants were constructed. The mutants showed attenuated growth in response to in vitro stress conditions that mimic the intracellular milieu. Our data sheds new light on the function of a novel regulon controlled by Rv1404 that coordinates adaptation of M. tuberculosis to the in vivo environment and reveals the Rv1405c and Rv1403c methyltransferases as playing a role in this adaptive process.

  12. CRTCs: an Essential Coactivator Family of CREB Regulated Transcription%cAMP-CREB信号转录通路新成员:CRTCs的研究进展

    Institute of Scientific and Technical Information of China (English)

    陈亚琼; 刘浥

    2010-01-01

    CRTCs(CREB Regulated Transcription Coactivator)是一个保守的真核蛋白质家族.作为CREB(CRE response element-binding protein)转录调控的必须共激活因子,CRTCs能与CREB结合并极强地增加后者的活性.同时作为cAMP-CREB信号转录通路的新成员,CRTCs能在细胞核质间穿梭并整合多个通路的信号,把细胞内外的信号直接传递到基因的转录活性.已经证实CRTC家族中的CRTC2在糖脂代谢调节及其相关疾病,特别是2型糖尿病的发生发展起着重要的作用.由于靶点明确,作用机制清楚,CRTC2及上游特异的调控因子有希望成为新的T2D治疗靶点.本文综述近年来CRTCs的研究成果,总结了CRTC2的发现、结构及分子机制.

  13. Transcription of a zebrafish gene of the hairy-Enhancer of split family delineates the midbrain anlage in the neural plate.

    Science.gov (United States)

    Müller, M; von Weizsäcker, E; Campos-Ortega, J A

    1996-09-01

    her5 encodes a basic helix-loop-helix (bHLH) protein with all features characteristic of the Drosophila hairy-E(spl) family. her5 is expressed in a band of cells within the neural anlage from about 90% epiboly on to at least 36 h postfertilization (hpf). After completion of brain morphogenesis, her5-expressing cells are located in the caudal region of the midbrain, at the boundary with the rhombencephalon. Labelling of cells within the her5 expression domain in the neural plate by injection of fluorescein-dextran allows their labelled progeny to be localized in the 36-hpf-old embryo using an anti-fluorescein antibody. This shows that the her5 expression domain corresponds to the midbrain primordium, including both the tectum and the tegmentum, in the neural plate. A possible function for her5 in regionalization of the brain and/or control of the midbrain-hindbrain boundary is discussed.

  14. NAC transcription factors: structurally distinct, functionally diverse

    DEFF Research Database (Denmark)

    Olsen, Addie Nina; Ernst, Heidi A; Leggio, Leila Lo;

    2005-01-01

    NAC proteins constitute one of the largest families of plant-specific transcription factors, and the family is present in a wide range of land plants. Here, we summarize the biological and molecular functions of the NAC family, paying particular attention to the intricate regulation of NAC protei...

  15. Transcription elongation

    Science.gov (United States)

    Imashimizu, Masahiko; Shimamoto, Nobuo; Oshima, Taku; Kashlev, Mikhail

    2014-01-01

    Regulation of transcription elongation via pausing of RNA polymerase has multiple physiological roles. The pausing mechanism depends on the sequence heterogeneity of the DNA being transcribed, as well as on certain interactions of polymerase with specific DNA sequences. In order to describe the mechanism of regulation, we introduce the concept of heterogeneity into the previously proposed alternative models of elongation, power stroke and Brownian ratchet. We also discuss molecular origins and physiological significances of the heterogeneity. PMID:25764114

  16. Bioinformatic Analyses of Subgroup-A Members of the Wheat bZIP Transcription Factor Family and Functional Identification of TabZIP174 Involved in Drought Stress Response

    Directory of Open Access Journals (Sweden)

    Xueyin Li

    2016-11-01

    Full Text Available Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses. Gene structure analysis showed that TabZIP genes with close phylogenetic relationships tended to possess similar exon-intron compositions, and the positions of introns in the hinge regions of the bZIP domains were highly conserved, whereas introns in the leucine zipper regions were at variable positions. Additionally, eleven groups of homologs and two groups of tandem paralogs were also identified in Subgroup A of the wheat bZIP family. Expression profiling analysis indicated that most Subgroup-A TabZIP genes were responsive to abscisic acid and various abiotic stress treatments. TabZIP27, TabZIP74, TabZIP138 and TabZIP174 proteins were localized in the nucleus of wheat protoplasts, whereas TabZIP9-GFP fusion protein was simultaneously present in the nucleus, cytoplasm and cell membrane. Transgenic Arabidopsis overexpressing TabZIP174 displayed increased seed germination rates and primary root lengths under drought treatments. Overexpression of TabZIP174 in transgenic Arabidopsis conferred enhanced drought tolerance, and transgenic plants exhibited lower water loss rates, higher survival rates, higher proline, soluble sugar and leaf

  17. Bioinformatic Analyses of Subgroup-A Members of the Wheat bZIP Transcription Factor Family and Functional Identification of TabZIP174 Involved in Drought Stress Response.

    Science.gov (United States)

    Li, Xueyin; Feng, Biane; Zhang, Fengjie; Tang, Yimiao; Zhang, Liping; Ma, Lingjian; Zhao, Changping; Gao, Shiqing

    2016-01-01

    Extensive studies in Arabidopsis and rice have demonstrated that Subgroup-A members of the bZIP transcription factor family play important roles in plant responses to multiple abiotic stresses. Although common wheat (Triticum aestivum) is one of the most widely cultivated and consumed food crops in the world, there are limited investigations into Subgroup A of the bZIP family in wheat. In this study, we performed bioinformatic analyses of the 41 Subgroup-A members of the wheat bZIP family. Phylogenetic and conserved motif analyses showed that most of the Subgroup-A bZIP proteins involved in abiotic stress responses of wheat, Arabidopsis, and rice clustered in Clade A1 of the phylogenetic tree, and shared a majority of conserved motifs, suggesting the potential importance of Clade-A1 members in abiotic stress responses. Gene structure analysis showed that TabZIP genes with close phylogenetic relationships tended to possess similar exon-intron compositions, and the positions of introns in the hinge regions of the bZIP domains were highly conserved, whereas introns in the leucine zipper regions were at variable positions. Additionally, eleven groups of homologs and two groups of tandem paralogs were also identified in Subgroup A of the wheat bZIP family. Expression profiling analysis indicated that most Subgroup-A TabZIP genes were responsive to abscisic acid and various abiotic stress treatments. TabZIP27, TabZIP74, TabZIP138, and TabZIP174 proteins were localized in the nucleus of wheat protoplasts, whereas TabZIP9-GFP fusion protein was simultaneously present in the nucleus, cytoplasm, and cell membrane. Transgenic Arabidopsis overexpressing TabZIP174 displayed increased seed germination rates and primary root lengths under drought treatments. Overexpression of TabZIP174 in transgenic Arabidopsis conferred enhanced drought tolerance, and transgenic plants exhibited lower water loss rates, higher survival rates, higher proline, soluble sugar, and leaf chlorophyll

  18. Probing the electrostatics and pharmacological modulation of sequence-specific binding by the DNA-binding domain of the ETS family transcription factor PU.1: a binding affinity and kinetics investigation.

    Science.gov (United States)

    Munde, Manoj; Poon, Gregory M K; Wilson, W David

    2013-05-27

    Members of the ETS family of transcription factors regulate a functionally diverse array of genes. All ETS proteins share a structurally conserved but sequence-divergent DNA-binding domain, known as the ETS domain. Although the structure and thermodynamics of the ETS-DNA complexes are well known, little is known about the kinetics of sequence recognition, a facet that offers potential insight into its molecular mechanism. We have characterized DNA binding by the ETS domain of PU.1 by biosensor-surface plasmon resonance (SPR). SPR analysis revealed a striking kinetic profile for DNA binding by the PU.1 ETS domain. At low salt concentrations, it binds high-affinity cognate DNA with a very slow association rate constant (≤10(5)M(-)(1)s(-)(1)), compensated by a correspondingly small dissociation rate constant. The kinetics are strongly salt dependent but mutually balance to produce a relatively weak dependence in the equilibrium constant. This profile contrasts sharply with reported data for other ETS domains (e.g., Ets-1, TEL) for which high-affinity binding is driven by rapid association (>10(7)M(-)(1)s(-)(1)). We interpret this difference in terms of the hydration properties of ETS-DNA binding and propose that at least two mechanisms of sequence recognition are employed by this family of DNA-binding domain. Additionally, we use SPR to demonstrate the potential for pharmacological inhibition of sequence-specific ETS-DNA binding, using the minor groove-binding distamycin as a model compound. Our work establishes SPR as a valuable technique for extending our understanding of the molecular mechanisms of ETS-DNA interactions as well as developing potential small-molecule agents for biotechnological and therapeutic purposes.

  19. The 5S rDNA gene family in mollusks: characterization of transcriptional regulatory regions, prediction of secondary structures, and long-term evolution, with special attention to Mytilidae mussels.

    Science.gov (United States)

    Vizoso, Miguel; Vierna, Joaquín; González-Tizón, Ana M; Martínez-Lage, Andrés

    2011-01-01

    Several reports on the characterization of 5S ribosomal DNA (5S rDNA) in various animal groups have been published to date, but there is a lack of studies analyzing this gene family in a much broader context. Here, we have studied 5S rDNA variation in several molluskan species, including bivalves, gastropods, and cephalopods. The degree of conservation of transcriptional regulatory regions was analyzed in these lineages, revealing a conserved TATA-like box in the upstream region. The evolution of the 120 bp coding region (5S) was also studied, suggesting the occurrence of paralogue groups in razor clams, clams, and cockles. In addition, 5S rDNA sequences from 11 species and 7 genus of Mytilidae Rafinesque, 1815 mussels were sampled and studied in detail. Four different 5S rDNA types, based on the nontranscribed spacer region were identified. The phylogenetic analyses performed within each type showed a between-species gene clustering pattern, suggesting ancestral polymorphism. Moreover, some putative pseudogenized 5S copies were also identified. Our report, together with previous studies that found high degree of intragenomic divergence in bivalve species, suggests that birth-and-death evolution may be the main force driving the evolution of 5S rDNA in these animals, even at the genus level.

  20. Transcriptional regulation of SlPYL, SlPP2C, and SlSnRK2 gene families encoding ABA signal core components during tomato fruit development and drought stress.

    Science.gov (United States)

    Sun, Liang; Wang, Yan-Ping; Chen, Pei; Ren, Jie; Ji, Kai; Li, Qian; Li, Ping; Dai, Sheng-Jie; Leng, Ping

    2011-11-01

    In order to characterize the potential transcriptional regulation of core components of abscisic acid (ABA) signal transduction in tomato fruit development and drought stress, eight SlPYL (ABA receptor), seven SlPP2C (type 2C protein phosphatase), and eight SlSnRK2 (subfamily 2 of SNF1-related kinases) full-length cDNA sequences were isolated from the tomato nucleotide database of NCBI GenBank. All SlPYL, SlPP2C, and SlSnRK2 genes obtained are homologous to Arabidopsis AtPYL, AtPP2C, and AtSnRK2 genes, respectively. Based on phylogenetic analysis, SlPYLs and SlSnRK2s were clustered into three subfamilies/subclasses, and all SlPP2Cs belonged to PP2C group A. Within the SlPYL gene family, SlPYL1, SlPYL2, SlPYL3, and SlPYL6 were the major genes involved in the regulation of fruit development. Among them, SlPYL1 and SlPYL2 were expressed at high levels throughout the process of fruit development and ripening; SlPYL3 was strongly expressed at the immature green (IM) and mature green (MG) stages, while SlPYL6 was expressed strongly at the IM and red ripe (RR) stages. Within the SlPP2C gene family, the expression of SlPP2C, SlPP2C3, and SlPP2C4 increased after the MG stage; SlPP2C1 and SlPP2C5 peaked at the B3 stage, while SlPP2C2 and SlPP2C6 changed little during fruit development. Within the SlSnRK2 gene family, the expression of SlSnRK2.2, SlSnRK2.3, SlSnRK2.4, and SlSnRK2C was higher than that of other members during fruit development. Additionally, most SlPYL genes were down-regulated, while most SlPP2C and SlSnRK2 genes were up-regulated by dehydration in tomato leaf.

  1. Transcriptional factors, Mafs and their biological roles

    Institute of Scientific and Technical Information of China (English)

    Mariko Tsuchiya; Ryoichi Misaka; Kosaku Nitta; Ken Tsuchiya

    2015-01-01

    The Maf family of transcription factors is characterizedby a typical bZip structure; these transcription factorsact as important regulators of the development anddifferentiation of many organs and tissues, includingthe kidney. The Maf family consists of two subgroupsthat are characterized according to their structure largeMaf transcription factors and small Maf transcriptionfactors. The large Maf subgroup consists of fourproteins, designated as MAFA, MAFB, c-MAF and neuralretina-specific leucine zipper. In particular, MAFA is adistinct molecule that has been attracting the attentionof researchers because it acts as a strong transactivatorof insulin, suggesting that Maf transcription factors arelikely to be involved in systemic energy homeostasis. Inthis review, we focused on the regulation of glucose/energy balance by Maf transcription factors in variousorgans.

  2. DBD: a transcription factor prediction database.

    Science.gov (United States)

    Kummerfeld, Sarah K; Teichmann, Sarah A

    2006-01-01

    Regulation of gene expression influences almost all biological processes in an organism; sequence-specific DNA-binding transcription factors are critical to this control. For most genomes, the repertoire of transcription factors is only partially known. Hitherto transcription factor identification has been largely based on genome annotation pipelines that use pairwise sequence comparisons, which detect only those factors similar to known genes, or on functional classification schemes that amalgamate many types of proteins into the category of 'transcription factor'. Using a novel transcription factor identification method, the DBD transcription factor database fills this void, providing genome-wide transcription factor predictions for organisms from across the tree of life. The prediction method behind DBD identifies sequence-specific DNA-binding transcription factors through homology using profile hidden Markov models (HMMs) of domains. Thus, it is limited to factors that are homologus to those HMMs. The collection of HMMs is taken from two existing databases (Pfam and SUPERFAMILY), and is limited to models that exclusively detect transcription factors that specifically recognize DNA sequences. It does not include basal transcription factors or chromatin-associated proteins, for instance. Based on comparison with experimentally verified annotation, the prediction procedure is between 95% and 99% accurate. Between one quarter and one-half of our genome-wide predicted transcription factors represent previously uncharacterized proteins. The DBD (www.transcriptionfactor.org) consists of predicted transcription factor repertoires for 150 completely sequenced genomes, their domain assignments and the hand curated list of DNA-binding domain HMMs. Users can browse, search or download the predictions by genome, domain family or sequence identifier, view families of transcription factors based on domain architecture and receive predictions for a protein sequence.

  3. 大豆GH3家族三个成员对20种农药的转录响应%Twenty Pesticides-induced Transcription Expression of Three Genes ofGH3 Family in Soybean

    Institute of Scientific and Technical Information of China (English)

    徐明飞; 吴长兴; 苍涛; 陈丽萍; 陈列忠; 蔡磊明; 李岗

    2015-01-01

    植物GH3基因家族具有生长素(IAA)等植物激素的氨基酸化合成酶活性,参与调节IAA等的动态平衡,在植物生长发育和抗逆性方面具有重要作用。为了明确大豆GH3基因家族成员对主要农药的响应特点,用qRT-PCR分析了20种不同作用机制的农药对该家族XM003518758、XM003521754和XM003543231在60 min内的诱导特点。结果表明,XM003518758基因的表达受草甘膦、氰戊菊酯轻微抑制,受2甲4氯等其余18种农药诱导上调但不超过2.5倍。所有测试的20种农药均不抑制XM003521754基因的表达,而最大诱导表达量达10倍以上。2甲4氯、乙草胺、百草枯、氰戊菊酯和戊唑醇对XM003543231诱导表达超过50倍,而其余15种测试农药对XM003543231的表达无抑制效应。而大豆XM003521754基因只受2甲4氯、二氯喹啉酸和多菌灵的显著诱导上调。%GH3 gene family plays prominent roles in plant development and stress resistance through maintain-ing phytohormone homeostasis depended on their IAA-amido synthetase activity. In order to explore the ex-pression patterns in transcription level of the soybeanGH3 gene family, we used qRT-PCR to determine the re-sponse of the three members of the family,XM003518758, XM003521754 andXM003543231, after exposure to 20 pesticides within 60 minutes. The expression ofXM003518758 was slightly depressed by glyphosate and cy-halothrin, and induced no more than 2.5 times by the other 18 pesticides tested. All 20 pesticides tested were not depressed the expression ofXM003521754 and some of them induced theXM003521754 expression over 10 times. Over 50 times up-regulated expression ofXM003543231 was induced by MCPA, acetochlor, gramox-one, cyhalothrin, and tebuconazole, while the other 15 pesticides tested had not depressed-effect on the expres-sion ofXM003543231. It was important that the geneXM003521754 was induced only by auxin-like pesticides as MCPA, quinclorac, carbendazim.

  4. Paths of lateral gene transfer of lysyl-aminoacyl-tRNA synthetases with a unique evolutionary transition stage of prokaryotes coding for class I and II varieties by the same organisms

    Directory of Open Access Journals (Sweden)

    Nussinov Ruth

    2006-03-01

    Full Text Available Abstract Background While the premise that lateral gene transfer (LGT is a dominant evolutionary force is still in considerable dispute, the case for widespread LGT in the family of aminoacyl-tRNA synthetases (aaRS is no longer contentious. aaRSs are ancient enzymes, guarding the fidelity of the genetic code. They are clustered in two structurally unrelated classes. Only lysine aminoacyl-tRNA synthetase (LysRS is found both as a class 1 and a class 2 enzyme (LysRS1-2. Remarkably, in several extant prokaryotes both classes of the enzyme coexist, a unique phenomenon that has yet to receive its due attention. Results We applied a phylogenetic approach for determining the extent and origin of LGT in prokaryotic LysRS. Reconstructing species trees for Archaea and Bacteria, and inferring that their last common ancestors encoded LysRS1 and LysRS2, respectively, we studied the gains and losses of both classes. A complex pattern of LGT events emerged. In specific groups of organisms LysRS1 was replaced by LysRS2 (and vice versa. In one occasion, within the alpha proteobacteria, a LysRS2 to LysRS1 LGT was followed by reversal to LysRS2. After establishing the most likely LGT paths, we studied the possible origins of the laterally transferred genes. To this end, we reconstructed LysRS gene trees and evaluated the likely origins of the laterally transferred genes. While the sources of LysRS1 LGTs were readily identified, those for LysRS2 remain, for now, uncertain. The replacement of one LysRS by another apparently transits through a stage simultaneously coding for both synthetases, probably conferring a selective advantage to the affected organisms. Conclusion The family of LysRSs features complex LGT events. The currently available data were sufficient for identifying unambiguously the origins of LysRS1 but not of LysRS2 gene transfers. A selective advantage is suggested to organisms encoding simultaneously LysRS1-2.

  5. The Journey of a Transcription Factor

    DEFF Research Database (Denmark)

    Pireyre, Marie

    Plants have developed astonishing networks regulating their metabolism to adapt to their environment. The complexity of these networks is illustrated by the expansion of families of regulators such as transcription factors in the plant kingdom. Transcription factors specifically impact...... transcriptional networks by integrating exogenous and endogenous stimuli and regulating gene expression accordingly. Regulation of transcription factors and their activation is thus highly important to modulate the transcriptional programs and increase fitness of the plant in a given environment. Plant metabolism...... is regulated to allocate resources to growth and/or defense at different time points. Among plant chemical defenses are the amino acid-derived glucosinolates (GLS). Their absolute and relative accumulation is tightly regulated at basal level, but also in response to e.g. pathogen attack and hormone stimuli...

  6. Transcriptional Regulation of Plant Secondary Metabolism

    Institute of Scientific and Technical Information of China (English)

    Chang-Qing Yang; Xin Fang; Xiu-Ming Wu; Ying-Bo Mao; Ling-Jian Wang; Xiao-Ya Chen

    2012-01-01

    Plant secondary metabolites play critical roles in plant-environment interactions.They are synthesized in different organs or tissues at particular developmental stages,and in response to various environmental stimuli,both biotic and abiotic.Accordingly,corresponding genes are regulated at the transcriptional level by multiple transcription factors.Several families of transcription factors have been identified to participate in controlling the biosynthesis and accumulation of secondary metabolites.These regulators integrate internal (often developmental) and external signals,bind to corresponding cis-elements — which are often in the promoter regions — to activate or repress the expression of enzyme-coding genes,and some of them interact with other transcription factors to form a complex.In this review,we summarize recent research in these areas,with an emphasis on newly-identified transcription factors and their functions in metabolism regulation.

  7. Identification and characterization of two gcvA genes in Sinorhizobium meliloti

    Institute of Scientific and Technical Information of China (English)

    QI MingSheng; LUO Li; CHENG HaiPing; ZHU JiaBi; YU GuanQiao

    2009-01-01

    GcvA is a member of the LysR family of transcriptional regulators that mediates the expression of the glycine cleavage (GCV) operon (gcvTHP) in response to glycine in Escherichia coil In our previous work, 90 putative regulator genes of the LysR family in Sinorhizobium meliloti were mutagenized to determine their phenotype. In the present study, we found that the S. mefiloti genome had two gcvA genes, gcvA1 and gcvA2. Both gcvA1 and gcvA2were required for full activation of the gcvTHPoperon in the presence of exogenous glycine. The gcvA1-mediated activation of gcvTHP operon was gly-cine-inducible, while gcvA2-mediated activation was not. We speculate that the regulatory mechanism for gcvTHP expression in S. meliloti differed from E. coiL Evolutionary analysis showed that GcvA were distributed in many genera of Proteobacteria and the distances between GcvA1 and GcvA2 in S. meliloti and GcvA in E. coil were large, which may explain the different regulatory mechanisms for gcvTHP expression. These findings could provide new clues to the role of the LysR gene family.

  8. CHD chromatin remodelers and the transcription cycle.

    Science.gov (United States)

    Murawska, Magdalena; Brehm, Alexander

    2011-01-01

    It is well established that ATP-dependent chromatin remodelers modulate DNA access of transcription factors and RNA polymerases by "opening" or "closing" chromatin structure. However, this view is far too simplistic. Recent findings have demonstrated that these enzymes not only set the stage for the transcription machinery to act but are actively involved at every step of the transcription process. As a consequence, they affect initiation, elongation, termination and RNA processing. In this review we will use the CHD family as a paradigm to illustrate the progress that has been made in revealing these new concepts.

  9. Boosting transcription by transcription: enhancer-associated transcripts.

    Science.gov (United States)

    Darrow, Emily M; Chadwick, Brian P

    2013-12-01

    Enhancers are traditionally viewed as DNA sequences located some distance from a promoter that act in cis and in an orientation-independent fashion to increase utilization of specific promoters and thereby regulate gene expression. Much progress has been made over the last decade toward understanding how these distant elements interact with target promoters, but how transcription is enhanced remains an object of active inquiry. Recent reports convey the prevalence and diversity of enhancer transcription and transcripts and support both as key factors with mechanistically distinct, but not mutually exclusive roles in enhancer function. Decoupling the causes and effects of transcription on the local chromatin landscape and understanding the role of enhancer transcripts in the context of long-range interactions are challenges that require additional attention. In this review, we focus on the possible functions of enhancer transcription by highlighting several recent enhancer RNA papers and, within the context of other enhancer studies, speculate on the role of enhancer transcription in regulating differential gene expression.

  10. Colon cancer associated transcripts in human cancers.

    Science.gov (United States)

    Chen, Yincong; Xie, Haibiao; Gao, Qunjun; Zhan, Hengji; Xiao, Huizhong; Zou, Yifan; Zhang, Fuyou; Liu, Yuchen; Li, Jianfa

    2017-08-02

    Long non-coding RNAs serve as important regulators in complicated cellular activities, including cell differentiation, proliferation and death. Dysregulation of long non-coding RNAs occurs in the formation and progression of cancers. The family of colon cancer associated transcripts, long non-coding RNAs colon cancer associated transcript-1 and colon cancer associated transcript-2 are known as oncogenes involved in various cancers. Colon cancer associated transcript-1 is a novel lncRNA located in 8q24.2, and colon cancer associated transcript-2 maps to the 8q24.21 region encompassing rs6983267. Colon cancer associated transcripts have close associations with clinical characteristics, such as lymph node metastasis, high TNM stage and short overall survival. Knockdown of them can reverse the malignant phenotypes of cancer cells, including proliferation, migration, invasion and apoptosis. Moreover, they can increase the expression level of c-MYC and oncogenic microRNAs via activating a series of complex mechanisms. In brief, the family of colon cancer associated transcripts may serve as potential biomarkers or therapeutic targets for human cancers. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  11. Arabidopsis transcription factors: genome-wide comparative analysis among eukaryotes.

    Science.gov (United States)

    Riechmann, J L; Heard, J; Martin, G; Reuber, L; Jiang, C; Keddie, J; Adam, L; Pineda, O; Ratcliffe, O J; Samaha, R R; Creelman, R; Pilgrim, M; Broun, P; Zhang, J Z; Ghandehari, D; Sherman, B K; Yu, G

    2000-12-15

    The completion of the Arabidopsis thaliana genome sequence allows a comparative analysis of transcriptional regulators across the three eukaryotic kingdoms. Arabidopsis dedicates over 5% of its genome to code for more than 1500 transcription factors, about 45% of which are from families specific to plants. Arabidopsis transcription factors that belong to families common to all eukaryotes do not share significant similarity with those of the other kingdoms beyond the conserved DNA binding domains, many of which have been arranged in combinations specific to each lineage. The genome-wide comparison reveals the evolutionary generation of diversity in the regulation of transcription.

  12. Structural insights into transcription complexes.

    Science.gov (United States)

    Berger, Imre; Blanco, Alexandre G; Boelens, Rolf; Cavarelli, Jean; Coll, Miquel; Folkers, Gert E; Nie, Yan; Pogenberg, Vivian; Schultz, Patrick; Wilmanns, Matthias; Moras, Dino; Poterszman, Arnaud

    2011-08-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of structural proteomics on our understanding of the molecular basis of gene expression. While most atomic structures were obtained by X-ray crystallography, the impact of solution NMR and cryo-electron microscopy is far from being negligible. Here, we summarize some highlights and illustrate the importance of specific technologies on the structural biology of protein-protein or protein/DNA transcription complexes: structure/function analysis of components the eukaryotic basal and activated transcription machinery with focus on the TFIID and TFIIH multi-subunit complexes as well as transcription regulators such as members of the nuclear hormone receptor families. We also discuss molecular aspects of promoter recognition and epigenetic control of gene expression. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Plant NAC-type transcription factor proteins contain a NARD domain for repression of transcriptional activation.

    Science.gov (United States)

    Hao, Yu-Jun; Song, Qing-Xin; Chen, Hao-Wei; Zou, Hong-Feng; Wei, Wei; Kang, Xu-Sheng; Ma, Biao; Zhang, Wan-Ke; Zhang, Jin-Song; Chen, Shou-Yi

    2010-10-01

    Plant-specific transcription factor NAC proteins play essential roles in many biological processes such as development, senescence, morphogenesis, and stress signal transduction pathways. In the NAC family, some members function as transcription activators while others act as repressors. In the present study we found that though the full-length GmNAC20 from soybean did not have transcriptional activation activity, the carboxy-terminal activation domain of GmNAC20 had high transcriptional activation activity in the yeast assay system. Deletion experiments revealed an active repression domain with 35 amino acids, named NARD (NAC Repression Domain), in the d subdomain of NAC DNA-binding domain. NARD can reduce the transcriptional activation ability of diverse transcription factors when fused to either the amino-terminal or the carboxy-terminal of the transcription factors. NARD-like sequences are also present in other NAC family members and they are functional repression domain when fused to VP16 in plant protoplast assay system. Mutation analysis of conserved amino acid residues in NARD showed that the hydrophobic LVFY motif may partially contribute to the repression function. It is hypothesized that the interactions between the repression domain NARD and the carboxy-terminal activation domain may finally determine the ability of NAC family proteins to regulate downstream gene expressions.

  14. Transcription in archaea

    Science.gov (United States)

    Kyrpides, N. C.; Ouzounis, C. A.; Woese, C. R. (Principal Investigator)

    1999-01-01

    Using the sequences of all the known transcription-associated proteins from Bacteria and Eucarya (a total of 4,147), we have identified their homologous counterparts in the four complete archaeal genomes. Through extensive sequence comparisons, we establish the presence of 280 predicted transcription factors or transcription-associated proteins in the four archaeal genomes, of which 168 have homologs only in Bacteria, 51 have homologs only in Eucarya, and the remaining 61 have homologs in both phylogenetic domains. Although bacterial and eukaryotic transcription have very few factors in common, each exclusively shares a significantly greater number with the Archaea, especially the Bacteria. This last fact contrasts with the obvious close relationship between the archaeal and eukaryotic transcription mechanisms per se, and in particular, basic transcription initiation. We interpret these results to mean that the archaeal transcription system has retained more ancestral characteristics than have the transcription mechanisms in either of the other two domains.

  15. Dynamic antagonism between phytochromes and PIF family basic helix-loop-helix factors induces selective reciprocal responses to light and shade in a rapidly responsive transcriptional network in Arabidopsis.

    Science.gov (United States)

    Leivar, Pablo; Tepperman, James M; Cohn, Megan M; Monte, Elena; Al-Sady, Bassem; Erickson, Erika; Quail, Peter H

    2012-04-01

    Plants respond to shade-modulated light signals via phytochrome (phy)-induced adaptive changes, termed shade avoidance. To examine the roles of Phytochrome-Interacting basic helix-loop-helix Factors, PIF1, 3, 4, and 5, in relaying such signals to the transcriptional network, we compared the shade-responsive transcriptome profiles of wild-type and quadruple pif (pifq) mutants. We identify a subset of genes, enriched in transcription factor-encoding loci, that respond rapidly to shade, in a PIF-dependent manner, and contain promoter G-box motifs, known to bind PIFs. These genes are potential direct targets of phy-PIF signaling that regulate the primary downstream transcriptional circuitry. A second subset of PIF-dependent, early response genes, lacking G-box motifs, are enriched for auxin-responsive loci, and are thus potentially indirect targets of phy-PIF signaling, mediating the rapid cell expansion induced by shade. Comparing deetiolation- and shade-responsive transcriptomes identifies another subset of G-box-containing genes that reciprocally display rapid repression and induction in response to light and shade signals. These data define a core set of transcriptional and hormonal processes that appear to be dynamically poised to react rapidly to light-environment changes via perturbations in the mutually antagonistic actions of the phys and PIFs. Comparing the responsiveness of the pifq and triple pif mutants to light and shade confirms that the PIFs act with overlapping redundancy on seedling morphogenesis and transcriptional regulation but that each PIF contributes differentially to these responses.

  16. Evolution of transcriptional networks in yeast: alternative teams of transcriptional factors for different species

    OpenAIRE

    Adriana Muñoz; Daniella Santos Muñoz; Aleksey Zimin; Yorke, James A.

    2016-01-01

    Background The diversity in eukaryotic life reflects a diversity in regulatory pathways. Nocedal and Johnson argue that the rewiring of gene regulatory networks is a major force for the diversity of life, that changes in regulation can create new species. Results We have created a method (based on our new “ping-pong algorithm) for detecting more complicated rewirings, where several transcription factors can substitute for one or more transcription factors in the regulation of a family of co-r...

  17. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  18. Dissolved families

    DEFF Research Database (Denmark)

    Christoffersen, Mogens

    The situation in the family preceding a family separation is studied here, to identify risk factors for family dissolution. Information registers covering prospective statistics about health aspects, demographic variables, family violence, self-destructive behaviour, unemployment, and the spousal...

  19. Family Life

    Science.gov (United States)

    ... With Family and Friends > Family Life Request Permissions Family Life Approved by the Cancer.Net Editorial Board , ... your outlook on the future. Friends and adult family members The effects of cancer on your relationships ...

  20. Comparison of Transcription Factor Binding Site Models

    KAUST Repository

    Bhuyan, Sharifulislam

    2012-05-01

    Modeling of transcription factor binding sites (TFBSs) and TFBS prediction on genomic sequences are important steps to elucidate transcription regulatory mechanism. Dependency of transcription regulation on a great number of factors such as chemical specificity, molecular structure, genomic and epigenetic characteristics, long distance interaction, makes this a challenging problem. Different experimental procedures generate evidence that DNA-binding domains of transcription factors show considerable DNA sequence specificity. Probabilistic modeling of TFBSs has been moderately successful in identifying patterns from a family of sequences. In this study, we compare performances of different probabilistic models and try to estimate their efficacy over experimental TFBSs data. We build a pipeline to calculate sensitivity and specificity from aligned TFBS sequences for several probabilistic models, such as Markov chains, hidden Markov models, Bayesian networks. Our work, containing relevant statistics and evaluation for the models, can help researchers to choose the most appropriate model for the problem at hand.

  1. A sensitive RNase protection assay to detect transcripts from potentially functional human endogenous L1 retrotransposons

    DEFF Research Database (Denmark)

    Woodcock, D M; Williamson, M R; Doherty, J P

    1996-01-01

    A high background of read-through transcripts from degenerate human L1 retrotransposons is present in almost all human cell types. This prevents the detection of RNA transcripts from potentially functional elements. To overcome this, we have developed an RNase protection assay based on the recons...... transcripts from divergent L1 families but are either discrete shorter transcripts or specifically processed products from longer initial transcripts....

  2. Mapping Yeast Transcriptional Networks

    OpenAIRE

    Hughes, Timothy R; de Boer, Carl G.

    2013-01-01

    The term “transcriptional network” refers to the mechanism(s) that underlies coordinated expression of genes, typically involving transcription factors (TFs) binding to the promoters of multiple genes, and individual genes controlled by multiple TFs. A multitude of studies in the last two decades have aimed to map and characterize transcriptional networks in the yeast Saccharomyces cerevisiae. We review the methodologies and accomplishments of these studies, as well as challenges we now face....

  3. A Nonnatural Transcriptional Coactivator

    Science.gov (United States)

    Nyanguile, Origene; Uesugi, Motonari; Austin, David J.; Verdine, Gregory L.

    1997-12-01

    In eukaryotes, sequence-specific DNA-binding proteins activate gene expression by recruiting the transcriptional apparatus and chromatin remodeling proteins to the promoter through protein-protein contacts. In many instances, the connection between DNA-binding proteins and the transcriptional apparatus is established through the intermediacy of adapter proteins known as coactivators. Here we describe synthetic molecules with low molecular weight that act as transcriptional coactivators. We demonstrate that a completely nonnatural activation domain in one such molecule is capable of stimulating transcription in vitro and in vivo. The present strategy provides a means of gaining external control over gene activation through intervention using small molecules.

  4. Massively Systematic Transcript End Readout (MASTER): Transcription Start Site Selection, Transcriptional Slippage, and Transcript Yields

    Science.gov (United States)

    Vvedenskaya, Irina O.; Zhang, Yuanchao; Goldman, Seth R.; Valenti, Anna; Visone, Valeria; Taylor, Deanne M.; Ebright, Richard H.; Nickels, Bryce E.

    2015-01-01

    SUMMARY We report the development of a next-generation sequencing-based technology that entails construction of a DNA library comprising up to at least 47 (~16,000) bar-coded sequences, production of RNA transcripts, and analysis of transcript ends and transcript yields ("massively systematic transcript end readout," MASTER). Using MASTER, we define full inventories of transcription start sites ("TSSomes") of Escherichia coli RNA polymerase for initiation at a consensus core promoter in vitro and in vivo, we define the TSS-region DNA-sequence determinants for TSS selection, reiterative initiation ("slippage synthesis"), and transcript yield, and we define effects of DNA topology and NTP concentration. The results reveal that slippage synthesis occurs from the majority of TSS-region DNA sequences and that TSS-region DNA sequences have profound, up to 100-fold, effects on transcript yield. The results further reveal that TSSomes depend on DNA topology, consistent with the proposal that TSS selection involves transcription-bubble expansion ("scrunching") and transcription-bubble contraction ("anti-scrunching"). PMID:26626484

  5. Massively Systematic Transcript End Readout, "MASTER": Transcription Start Site Selection, Transcriptional Slippage, and Transcript Yields.

    Science.gov (United States)

    Vvedenskaya, Irina O; Zhang, Yuanchao; Goldman, Seth R; Valenti, Anna; Visone, Valeria; Taylor, Deanne M; Ebright, Richard H; Nickels, Bryce E

    2015-12-17

    We report the development of a next-generation sequencing-based technology that entails construction of a DNA library comprising up to at least 4(7) (∼ 16,000) barcoded sequences, production of RNA transcripts, and analysis of transcript ends and transcript yields (massively systematic transcript end readout, "MASTER"). Using MASTER, we define full inventories of transcription start sites ("TSSomes") of Escherichia coli RNA polymerase for initiation at a consensus core promoter in vitro and in vivo; we define the TSS-region DNA sequence determinants for TSS selection, reiterative initiation ("slippage synthesis"), and transcript yield; and we define effects of DNA topology and NTP concentration. The results reveal that slippage synthesis occurs from the majority of TSS-region DNA sequences and that TSS-region DNA sequences have profound, up to 100-fold, effects on transcript yield. The results further reveal that TSSomes depend on DNA topology, consistent with the proposal that TSS selection involves transcription-bubble expansion ("scrunching") and transcription-bubble contraction ("anti-scrunching").

  6. Isolation, classification and transcription profiles of the AP2/ERF transcription factor superfamily in citrus.

    Science.gov (United States)

    Xie, Xiu-lan; Shen, Shu-ling; Yin, Xue-ren; Xu, Qian; Sun, Chong-de; Grierson, Donald; Ferguson, Ian; Chen, Kun-song

    2014-07-01

    The AP2/ERF gene family encodes plant-specific transcription factors. In model plants, AP2/ERF genes have been shown to be expressed in response to developmental and environmental stimuli, and many function downstream of the ethylene, biotic, and abiotic stress signaling pathways. In citrus, ethylene is effective in regulation citrus fruit quality, such as degreening and aroma. However, information about the citrus AP2/ERF family is limited, and would enhance our understanding of fruit responses to environmental stress, fruit development and quality. CitAP2/ERF genes were isolated using the citrus genome database, and their expression patterns analyzed by real-time PCR using various orange organs and samples from a fruit developmental series. 126 sequences with homologies to AP2/ERF proteins were identified from the citrus genome, and, on the basis of their structure and sequence, assigned to the ERF family (102), AP2 family (18), RAV family (4) and Soloist (2). MEME motif analysis predicted the defining AP2/ERF domain and EAR repressor domains. Analysis of transcript accumulation in Citrus sinensis cv. 'Newhall' indicated that CitAP2/ERF genes show organ-specific and temporal expression, and provided a framework for understanding the transcriptional regulatory roles of AP2/ERF gene family members in citrus. Hierarchical cluster analysis and t tests identified regulators that potentially function during orange fruit growth and development.

  7. Regulation and evolution of malonate and propionate catabolism in proteobacteria.

    Science.gov (United States)

    Suvorova, I A; Ravcheev, D A; Gelfand, M S

    2012-06-01

    Bacteria catabolize malonate via two pathways, encoded by the mdc and mat genes. In various bacteria, transcription of these genes is controlled by the GntR family transcription factors (TFs) MatR/MdcY and/or the LysR family transcription factor MdcR. Propionate is metabolized via the methylcitrate pathway, comprising enzymes encoded by the prp and acn genes. PrpR, the Fis family sigma 54-dependent transcription factor, is known to be a transcriptional activator of the prp genes. Here, we report a detailed comparative genomic analysis of malonate and propionate metabolism and its regulation in proteobacteria. We characterize genomic loci and gene regulation and identify binding motifs for four new TFs and also new regulon members, in particular, tripartite ATP-independent periplasmic (TRAP) transporters. We describe restructuring of the genomic loci and regulatory interactions during the evolution of proteobacteria.

  8. Combinatorial analysis of lupulin gland transcription factors from R2R3Myb, bHLH and WDR families indicates a complex regulation of chs_H1 genes essential for prenylflavonoid biosynthesis in hop (Humulus Lupulus L.

    Directory of Open Access Journals (Sweden)

    Matoušek Jaroslav

    2012-02-01

    Full Text Available Abstract Background Lupulin glands of hop produce a specific metabolome including hop bitter acids valuable for the brewing process and prenylflavonoids with promising health-beneficial activities. The detailed analysis of the transcription factor (TF-mediated regulation of the oligofamily of one of the key enzymes, i.e., chalcone synthase CHS_H1 that efficiently catalyzes the production of naringenin chalcone, a direct precursor of prenylflavonoids in hop, constitutes an important part of the dissection of the biosynthetic pathways leading to the accumulation of these compounds. Results Homologues of flavonoid-regulating TFs HlMyb2 (M2, HlbHLH2 (B2 and HlWDR1 (W1 from hop were cloned using a lupulin gland-specific cDNA library from the hop variety Osvald's 72. Using a "combinatorial" transient GUS expression system it was shown that these unique lupulin-gland-associated TFs significantly activated the promoter (P of chs_H1 in ternary combinations of B2, W1 and either M2 or the previously characterized HlMyb3 (M3. The promoter activation was strongly dependent on the Myb-P binding box TCCTACC having a core sequence CCWACC positioned on its 5' end region and it seems that the complexity of the promoter plays an important role. M2B2W1-mediated activation significantly exceeded the strength of expression of native chs_H1 gene driven by the 35S promoter of CaMV, while M3B2W1 resulted in 30% of the 35S:chs_H1 expression level, as quantified by real-time PCR. Another newly cloned hop TF, HlMyb7, containing a transcriptional repressor-like motif pdLNLD/ELxiG/S (PDLNLELRIS, was identified as an efficient inhibitor of chs_H1-activating TFs. Comparative analyses of hop and A. thaliana TFs revealed a complex activation of Pchs_H1 and Pchs4 in combinatorial or independent manners. Conclusions This study on the sequences and functions of various lupulin gland-specific transcription factors provides insight into the complex character of the regulation of the

  9. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  10. The transcriptional landscape

    DEFF Research Database (Denmark)

    Nielsen, Henrik

    2011-01-01

    The application of new and less biased methods to study the transcriptional output from genomes, such as tiling arrays and deep sequencing, has revealed that most of the genome is transcribed and that there is substantial overlap of transcripts derived from the two strands of DNA. In protein codi...

  11. Research advance in tumors associated with microphthalmia-associated transcription factor gene family%小眼畸形转录因子基因家族相关肿瘤的分子病理研究进展

    Institute of Scientific and Technical Information of China (English)

    饶秋; 周晓军

    2011-01-01

    @@ 小眼畸形转录因子(microphthalmia-associated transcription factor,MiTF)位于3号染色体短臂(3p),是一种具有基本螺旋-环-螺旋-亮氨酸拉链(bHLHZip)结构的转录因子[1].研究表明MiTF在结构上与TFE3、TFEB和TFEC最接近.它们具有相似的DNA结合区域,即具有"CA[C/T]GTG"核心结构的DNA区域,并通过该结构与特异的DNA结构相结合,调控体内多种基因表达[1].

  12. Targeted deletion of murine CEACAM 1 activates PI3K-Akt signaling and contributes to the expression of (Pro)renin receptor via CREB family and NF-κB transcription factors.

    Science.gov (United States)

    Huang, Jiqian; Ledford, Kelly J; Pitkin, William B; Russo, Lucia; Najjar, Sonia M; Siragy, Helmy M

    2013-08-01

    The carcinoembryonic antigen-related cell adhesion molecule 1 regulates insulin sensitivity by promoting hepatic insulin clearance. Mice bearing a null mutation of Ceacam1 gene (Cc1(-/-)) develop impaired insulin clearance followed by hyperinsulinemia and insulin resistance, in addition to visceral obesity and increased plasma fatty acids. Because insulin resistance is associated with increased blood pressure, we investigated whether they develop higher blood pressure with activated renal renin-angiotensin system and whether this is mediated, in part, by the upregulation of renal (pro)renin receptor (PRR) expression. Compared with age-matched wild-type littermates, Cc1(-/-) mice exhibited increased blood pressure with increased activation of renal renin-angiotensin systems and renal PRR expression. Cytoplasmic and nuclear immunostaining of phospho-PI3K p85α and phospho-Akt was enhanced in the kidney of Cc1(-/-) mice. In murine renal inner medullary collecting duct epithelial cells with lentiviral-mediated small hairpin RNA knockdown of carcinoembryonic antigen-related cell adhesion molecule 1, PRR expression was upregulated and phosphorylation of PI3K (Tyr508), Akt (Ser473), NF-κB p65 (Ser276), cAMP response element-binding protein/activated transcription factor (ATF)-1 (Ser133), and ATF-2 (Thr71) was enhanced. Inhibiting PI3K with LY294002 or Akt with Akt inhibitor VIII attenuated PRR expression. In conclusion, global null deletion of Ceacam1 caused an increase in blood pressure with increased renin-angiotensin system activation together with upregulation of PRR via PI3K-Akt activation of cAMP response element-binding protein 1, ATF-1, ATF-2, and NF-κB p65 transcription factors.

  13. Mechanical Properties of Transcription

    Science.gov (United States)

    Sevier, Stuart A.; Levine, Herbert

    2017-06-01

    The mechanical properties of transcription have recently been shown to play a central role in gene expression. However, a full physical characterization of this central biological process is lacking. In this Letter, we introduce a simple description of the basic physical elements of transcription where RNA elongation, RNA polymerase rotation, and DNA supercoiling are coupled. The resulting framework describes the relative amount of RNA polymerase rotation and DNA supercoiling that occurs during RNA elongation. Asymptotic behavior is derived and can be used to experimentally extract unknown mechanical parameters of transcription. Mechanical limits to transcription are incorporated through the addition of a DNA supercoiling-dependent RNA polymerase velocity. This addition can lead to transcriptional stalling and resulting implications for gene expression, chromatin structure and genome organization are discussed.

  14. Family Therapy

    Science.gov (United States)

    ... may be credentialed by the American Association for Marriage and Family Therapy (AAMFT). Family therapy is often short term. ... challenging situations in a more effective way. References Marriage and family therapists: The friendly mental health professionals. American Association ...

  15. Familial hypertriglyceridemia

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/000397.htm Familial hypertriglyceridemia To use the sharing features on this page, please enable JavaScript. Familial hypertriglyceridemia is a common disorder passed down through families. ...

  16. Family Meals

    Science.gov (United States)

    ... Teaching Kids to Be Smart About Social Media Family Meals KidsHealth > For Parents > Family Meals Print A ... even more important as kids get older. Making Family Meals Happen It can be a big challenge ...

  17. Family Arguments

    Science.gov (United States)

    ... Spread the Word Shop AAP Find a Pediatrician Family Life Medical Home Family Dynamics Adoption & Foster Care ... Life Listen Español Text Size Email Print Share Family Arguments Page Content Article Body We seem to ...

  18. Family History

    Science.gov (United States)

    Your family history includes health information about you and your close relatives. Families have many factors in common, including their genes, ... as heart disease, stroke, and cancer. Having a family member with a disease raises your risk, but ...

  19. Transcriptional profiling of UlaR-regulated genes in Streptococcus pneumoniae

    NARCIS (Netherlands)

    Shafeeq, Sulman; Afzal, Muhammad; Henriques-Normark, Birgitta; Kuipers, Oscar P

    2015-01-01

    The transcriptional regulator UlaR belongs to the family of PRD-containing transcriptional regulators, which are mostly involved in the regulation of carbohydrate metabolism. The role of the transcriptional regulator UlaR in Streptococcus pneumoniae has recently been described [1]. Here, we report d

  20. Effect of MITF Transcriptional Control on Family of Tyrosinase-related Proteins in Normal Human Melanocytes%正常人黑素细胞MITF对酪氨酸酶相关蛋白的转录调控研究

    Institute of Scientific and Technical Information of China (English)

    黎钊; 王平; 洪为松; 郑俊惠

    2013-01-01

    目的 研究正常人黑素细胞小眼畸形相关转录因子(MITF)对与黑素生成密切相关的酪氨酸酶相关蛋白(TRPs)家族的转录调控.方法 应用小RNA干扰技术(慢病毒感染),对培养的原代正常人黑素细胞进行MITF基因沉默,然后应用实时定量PCR和免疫印迹方法,分别检测MITF基因沉默前后,MITF、酪氨酸酶(TYR)、酪氨酸酶相关蛋白1(TYRP1)和酪氨酸酶相关蛋白2(TYRP2)的基因与蛋白表达水平.结果 正常人黑素细胞具有显著表达的MITF、TYR、TYRP1和TYRP2; MITF基因沉默后,MITF、TYR和TYRP1的基因表达水平分别下降2倍(P =0.001)、1.5倍(P=0.05)和5倍(P =0.005),TYRP2的表达水平上调3倍(P =0.004);而MITF基因沉默后的MITF、TYR、TYRP1的蛋白表达也显著下降,TYRP2蛋白显著升高.结论 黑素细胞TRPs家族与MITF转录调控密切相关,TYRP2可能存在不依赖于MITF的转录调控.%Objective To analyze the transcriptional control of microphthalmia transcription factor ( MITF) on the tyrosinase related proteins which is closely related to melanogenesis in normal human melanocytes. Methods Normal human melanocytes from healthy children's circumcision were cultured in melanocyte Hul6 selective medium. MITF was knocked down by using MITF siRNA interference. Real time quantitative PCR and Western blot were used to investigate the gene and proteins expression of MITF, tyrosinase( TYR) , tyrosinase related protein l(TYRPl)and tyrosinase related protein 2(TYRP2). Results The MITF, TYR, TYRP1 and TYRP2 were significant expressed in normal human melanocytes. After MITF was knocked down, we found that the expression of TYR and TYRP1 were dramatically decreased and the expression of TYRP2 was increased both in mRNA and protein expression. The mRNA expression of MITF, TYR and TYRP1 were decreased about 2 folds (P =0.001) , 1.5 folds (P =0.05)and 5 folds (P =0.005) respectively, while TYRP2 was increased dramatically 3 folds ( P = 0. 004

  1. Recurrent t(2;2) and t(2;8) translocations in rhabdomyosarcoma without the canonical PAX-FOXO1 fuse PAX3 to members of the nuclear receptor transcriptional coactivator family.

    Science.gov (United States)

    Sumegi, Janos; Streblow, Renae; Frayer, Robert W; Dal Cin, Paola; Rosenberg, Andrew; Meloni-Ehrig, Aurelia; Bridge, Julia A

    2010-03-01

    The fusion oncoproteins PAX3-FOXO1 [t(2;13)(q35;q14)] and PAX7-FOXO1 [t(1;13)(p36;q14)] typify alveolar rhabdomyosarcoma (ARMS); however, 20-30% of cases lack these specific translocations. In this study, cytogenetic and/or molecular characterization to include FISH, reverse transcription polymerase chain reaction (RT-PCR), and sequencing analyses of five rhabdomyosarcomas [four ARMS and one embryonal rhabdomyosarcoma (ERMS)] with novel, recurrent t(2;2)(p23;q35) or t(2;8)(q35;q13) revealed that these noncanonical translocations fuse PAX3 to NCOA1 or NCOA2, respectively. The PAX3-NCOA1 and PAX3-NCOA2 transcripts encode chimeric proteins composed of the paired-box and homeodomain DNA-binding domains of PAX3, and the CID domain, the Q-rich region, and the activation domain 2 (AD2) domain of NCOA1 or NCOA2. To investigate the biological function of these recurrent variant translocations, the coding regions of PAX3-NCOA1 and PAX3-NCOA2 cDNA constructs were introduced into expression vectors with tetracycline-regulated expression. Both fusion proteins showed transforming activity in the soft-agar assay. Deletion of the AD2 portion of the PAX3-NCOA fusion proteins reduced the transforming activity of each chimeric protein. Similarly, but with greater impact, CID domain deletion fully abrogated the transforming activity of the chimeric protein. These studies (1) expand our knowledge of PAX3 variant translocations in RMS with identification of a novel PAX3-NCOA2 fusion, (2) show that both PAX3-NCOA1 and PAX3-NCOA2 represent recurrent RMS rearrangements, (3) confirm the transforming activity of both translocation events and demonstrate the essentiality of intact AD2 and CID domains for optimal transforming activity, and (4) provide alternative approaches (FISH and RT-PCR) for detecting PAX-NCOA fusions in nondividing cells of RMS. The latter could potentially be used as aids in diagnostically challenging cases.

  2. Runx transcription factors in neuronal development

    Directory of Open Access Journals (Sweden)

    Shiga Takashi

    2008-08-01

    Full Text Available Abstract Runt-related (Runx transcription factors control diverse aspects of embryonic development and are responsible for the pathogenesis of many human diseases. In recent years, the functions of this transcription factor family in the nervous system have just begun to be understood. In dorsal root ganglion neurons, Runx1 and Runx3 play pivotal roles in the development of nociceptive and proprioceptive sensory neurons, respectively. Runx appears to control the transcriptional regulation of neurotrophin receptors, numerous ion channels and neuropeptides. As a consequence, Runx contributes to diverse aspects of the sensory system in higher vertebrates. In this review, we summarize recent progress in determining the role of Runx in neuronal development.

  3. Switching on cilia: transcriptional networks regulating ciliogenesis.

    Science.gov (United States)

    Choksi, Semil P; Lauter, Gilbert; Swoboda, Peter; Roy, Sudipto

    2014-04-01

    Cilia play many essential roles in fluid transport and cellular locomotion, and as sensory hubs for a variety of signal transduction pathways. Despite having a conserved basic morphology, cilia vary extensively in their shapes and sizes, ultrastructural details, numbers per cell, motility patterns and sensory capabilities. Emerging evidence indicates that this diversity, which is intimately linked to the different functions that cilia perform, is in large part programmed at the transcriptional level. Here, we review our understanding of the transcriptional control of ciliary biogenesis, highlighting the activities of FOXJ1 and the RFX family of transcriptional regulators. In addition, we examine how a number of signaling pathways, and lineage and cell fate determinants can induce and modulate ciliogenic programs to bring about the differentiation of distinct cilia types.

  4. The world according to GARP transcription factors.

    Science.gov (United States)

    Safi, Alaeddine; Medici, Anna; Szponarski, Wojciech; Ruffel, Sandrine; Lacombe, Benoît; Krouk, Gabriel

    2017-10-01

    Plant specific GARP transcription factor family (made of ARR-B and G2-like) contains genes with very diverse in planta functions: nutrient sensing, root and shoot development, floral transition, chloroplast development, circadian clock oscillation maintenance, hormonal transport and signaling. In this work we review: first, their structural but distant relationships with MYB transcription factors, second, their role in planta, third, the diversity of their Cis-regulatory elements, fourth, their potential protein partners. We conclude that the GARP family may hold keys to understand the interactions between nutritional signaling pathways (nitrogen and phosphate at least) and development. Understanding how plant nutrition and development are coordinated is central to understand how to adapt plants to an ever-changing environment. Consequently GARPs are likely to attract increasing research attentions, as they are likely at the crossroads of these fundamental processes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  6. Family Privilege

    Science.gov (United States)

    Seita, John R.

    2014-01-01

    Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

  7. DNA supercoiling during transcription.

    Science.gov (United States)

    Ma, Jie; Wang, Michelle D

    2016-11-01

    The twin-supercoiled-domain model describes how transcription can drive DNA supercoiling, and how DNA supercoiling, in turn plays an important role in regulating gene transcription. In vivo and in vitro experiments have disclosed many details of the complex interactions in this relationship, and recently new insights have been gained with the help of genome-wide DNA supercoiling mapping techniques and single molecule methods. This review summarizes the general mechanisms of the interplay between DNA supercoiling and transcription, considers the biological implications, and focuses on recent important discoveries and technical advances in this field. We highlight the significant impact of DNA supercoiling in transcription, but also more broadly in all processes operating on DNA.

  8. DNA supercoiling during transcription

    Science.gov (United States)

    Ma, Jie; Wang, Michelle D.

    2017-01-01

    The twin-supercoiled-domain model describes how transcription can drive DNA supercoiling, and how DNA supercoiling, in turn plays an important role in regulating gene transcription. In vivo and in vitro experiments have disclosed many details of the complex interactions in this relationship, and recently new insights have been gained with the help of genome-wide DNA supercoiling mapping techniques and single molecule methods. This review summarizes the general mechanisms of the interplay between DNA supercoiling and transcription, considers the biological implications, and focuses on recent important discoveries and technical advances in this field. We highlight the significant impact of DNA supercoiling in transcription, but also more broadly in all processes operating on DNA.

  9. Experimental determination of the evolvability of a transcription factor.

    Science.gov (United States)

    Maerkl, Sebastian J; Quake, Stephen R

    2009-11-03

    Sequence-specific binding of a transcription factor to DNA is the central event in any transcriptional regulatory network. However, relatively little is known about the evolutionary plasticity of transcription factors. For example, the exact functional consequence of an amino acid substitution on the DNA-binding specificity of most transcription factors is currently not predictable. Furthermore, although the major structural families of transcription factors have been identified, the detailed DNA-binding repertoires within most families have not been characterized. We studied the sequence recognition code and evolvability of the basic helix-loop-helix transcription factor family by creating all possible 95 single-point mutations of five DNA-contacting residues of Max, a human helix-loop-helix transcription factor and measured the detailed DNA-binding repertoire of each mutant. Our results show that the sequence-specific repertoire of Max accessible through single-point mutations is extremely limited, and we are able to predict 92% of the naturally occurring diversity at these positions. All naturally occurring basic regions were also found to be accessible through functional intermediates. Finally, we observed a set of amino acids that are functional in vitro but are not found to be used naturally, indicating that functionality alone is not sufficient for selection.

  10. A systematic survey in Arabidopsis thaliana of transcription factors that modulate circadian parameters

    Directory of Open Access Journals (Sweden)

    Merkle Thomas

    2008-04-01

    Full Text Available Abstract Background Plant circadian systems regulate various biological processes in harmony with daily environmental changes. In Arabidopsis thaliana, the underlying clock mechanism is comprised of multiple integrated transcriptional feedbacks, which collectively lead to global patterns of rhythmic gene expression. The transcriptional networks are essential within the clock itself and in its output pathway. Results Here, to expand understanding of transcriptional networks within and associated to the clock, we performed both an in silico analysis of transcript rhythmicity of transcription factor genes, and a pilot assessment of functional phenomics on the MYB, bHLH, and bZIP families. In our in silico analysis, we defined which members of these families express a circadian waveform of transcript abundance. Up to 20% of these families were over-represented as clock-controlled genes. To detect members that contribute to proper oscillator function, we systematically measured rhythmic growth via an imaging system in hundreds of misexpression lines targeting members of the transcription-factor families. Three transcription factors were found that conferred aberrant circadian rhythms when misexpressed: MYB3R2, bHLH69, and bHLH92. Conclusion Transcript abundance of many transcription factors in Arabidopsis oscillates in a circadian manner. Further, a developed pipeline assessed phenotypic contribution of a panel of transcriptional regulators in the circadian system.

  11. Gene Transcription Profile of the Detached Retina (An AOS Thesis)

    Science.gov (United States)

    Zacks, David N.

    2009-01-01

    Purpose: Separation of the neurosensory retina from the retinal pigment epithelium (RPE) yields many morphologic and functional consequences, including death of the photoreceptor cells, Müller cell hypertrophy, and inner retinal rewiring. Many of these changes are due to the separation-induced activation of specific genes. In this work, we define the gene transcription profile within the retina as a function of time after detachment. We also define the early activation of kinases that might be responsible for the detachment-induced changes in gene transcription. Methods: Separation of the retina from the RPE was induced in Brown-Norway rats by the injection of 1% hyaluronic acid into the subretinal space. Retinas were harvested at 1, 7, and 28 days after separation. Gene transcription profiles for each time point were determined using the Affymetrix Rat 230A gene microarray chip. Transcription levels in detached retinas were compared to those of nondetached retinas with the BRB-ArrayTools Version 3.6.0 using a random variance analysis of variance (ANOVA) model. Confirmation of the significant transcriptional changes for a subset of the genes was performed using microfluidic quantitative real-time polymerase chain reaction (qRT-PCR) assays. Kinase activation was explored using Western blot analysis to look for early phosphorylation of any of the 3 main families of mitogen-activated protein kinases (MAPK): the p38 family, the Janus kinase family, and the p42/p44 family. Results: Retinas separated from the RPE showed extensive alterations in their gene transcription profile. Many of these changes were initiated as early as 1 day after separation, with significant increases by 7 days. ANOVA analysis defined 144 genes that had significantly altered transcription levels as a function of time after separation when setting a false discovery rate at ≤0.1. Confirmatory RT-PCR was performed on 51 of these 144 genes. Differential transcription detected on the microarray

  12. Familial gigantism

    NARCIS (Netherlands)

    W.W. de Herder (Wouter)

    2012-01-01

    textabstractFamilial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  13. Familial gigantism

    Directory of Open Access Journals (Sweden)

    Wouter W. de Herder

    2012-01-01

    Full Text Available Familial GH-secreting tumors are seen in association with three separate hereditary clinical syndromes: multiple endocrine neoplasia type 1, Carney complex, and familial isolated pituitary adenomas.

  14. SoyDB: a knowledge database of soybean transcription factors

    Directory of Open Access Journals (Sweden)

    Valliyodan Babu

    2010-01-01

    Full Text Available Abstract Background Transcription factors play the crucial rule of regulating gene expression and influence almost all biological processes. Systematically identifying and annotating transcription factors can greatly aid further understanding their functions and mechanisms. In this article, we present SoyDB, a user friendly database containing comprehensive knowledge of soybean transcription factors. Description The soybean genome was recently sequenced by the Department of Energy-Joint Genome Institute (DOE-JGI and is publicly available. Mining of this sequence identified 5,671 soybean genes as putative transcription factors. These genes were comprehensively annotated as an aid to the soybean research community. We developed SoyDB - a knowledge database for all the transcription factors in the soybean genome. The database contains protein sequences, predicted tertiary structures, putative DNA binding sites, domains, homologous templates in the Protein Data Bank (PDB, protein family classifications, multiple sequence alignments, consensus protein sequence motifs, web logo of each family, and web links to the soybean transcription factor database PlantTFDB, known EST sequences, and other general protein databases including Swiss-Prot, Gene Ontology, KEGG, EMBL, TAIR, InterPro, SMART, PROSITE, NCBI, and Pfam. The database can be accessed via an interactive and convenient web server, which supports full-text search, PSI-BLAST sequence search, database browsing by protein family, and automatic classification of a new protein sequence into one of 64 annotated transcription factor families by hidden Markov models. Conclusions A comprehensive soybean transcription factor database was constructed and made publicly accessible at http://casp.rnet.missouri.edu/soydb/.

  15. Transcriptional regulation of bone and joint remodeling by NFAT

    OpenAIRE

    2010-01-01

    Osteoporosis and arthritis are highly prevalent diseases and a significant cause of morbidity and mortality worldwide. These diseases result from aberrant tissue remodeling leading to weak, fracture-prone bones or painful, dysfunctional joints. The nuclear factor of activated T cells (NFAT) transcription factor family controls diverse biologic processes in vertebrates. Here, we review the scientific evidence that links NFAT-regulated gene transcription to bone and joint pathology. A particula...

  16. Smad transcription factors.

    Science.gov (United States)

    Massagué, Joan; Seoane, Joan; Wotton, David

    2005-12-01

    Smad transcription factors lie at the core of one of the most versatile cytokine signaling pathways in metazoan biology-the transforming growth factor-beta (TGFbeta) pathway. Recent progress has shed light into the processes of Smad activation and deactivation, nucleocytoplasmic dynamics, and assembly of transcriptional complexes. A rich repertoire of regulatory devices exerts control over each step of the Smad pathway. This knowledge is enabling work on more complex questions about the organization, integration, and modulation of Smad-dependent transcriptional programs. We are beginning to uncover self-enabled gene response cascades, graded Smad response mechanisms, and Smad-dependent synexpression groups. Our growing understanding of TGFbeta signaling through the Smad pathway provides general principles for how animal cells translate complex inputs into concrete behavior.

  17. Familial dermographism.

    Science.gov (United States)

    Jedele, K B; Michels, V V

    1991-05-01

    Urticaria in response to various physical stimuli has been reported in sporadic and familial patterns. The most common of these physical urticarias, dermographism, is a localized urticarial response to stroking or scratching of the skin and has not been reported previously to be familial. A four-generation family with dermographism, probably inherited as an autosomal dominant trait, is presented along with a discussion of sporadic dermographism and other types of familial physical urticarias.

  18. Timing of transcriptional quiescence during gametogenesis is controlled by global histone H3K4 demethylation.

    Science.gov (United States)

    Xu, Mengshu; Soloveychik, Maria; Ranger, Mathieu; Schertzberg, Michael; Shah, Zarna; Raisner, Ryan; Venkatasubrahmanyan, Shivkumar; Tsui, Kyle; Gebbia, Marinella; Hughes, Tim; van Bakel, Harm; Nislow, Corey; Madhani, Hiten D; Meneghini, Marc D

    2012-11-13

    Gametes are among the most highly specialized cells produced during development. Although gametogenesis culminates in transcriptional quiescence in plants and animals, regulatory mechanisms controlling this are unknown. Here, we confirm that gamete differentiation in the single-celled yeast Saccharomyces cerevisiae is accompanied by global transcriptional shutoff following the completion of meiosis. We show that Jhd2, a highly conserved JARID1-family histone H3K4 demethylase, activates protein-coding gene transcription in opposition to this programmed transcriptional shutoff, sustaining the period of productive transcription during spore differentiation. Moreover, using genome-wide nucleosome, H3K4me, and transcript mapping experiments, we demonstrate that JHD2 globally represses intergenic noncoding transcription during this period. The widespread transcriptional defects of JHD2 mutants are associated with precocious differentiation and the production of stress-sensitive spores, demonstrating that Jhd2 regulation of the global postmeiotic transcriptional program is critical for the production of healthy meiotic progeny.

  19. The T box regulatory element controlling expression of the class I lysyl-tRNA synthetase of Bacillus cereus strain 14579 is functional and can be partially induced by reduced charging of asparaginyl-tRNAAsn

    LENUS (Irish Health Repository)

    Foy, Niall

    2010-07-22

    Abstract Background Lysyl-tRNA synthetase (LysRS) is unique within the aminoacyl-tRNA synthetase family in that both class I (LysRS1) and class II (LysRS2) enzymes exist. LysRS1 enzymes are found in Archaebacteria and some eubacteria while all other organisms have LysRS2 enzymes. All sequenced strains of Bacillus cereus (except AH820) and Bacillus thuringiensis however encode both a class I and a class II LysRS. The lysK gene (encoding LysRS1) of B. cereus strain 14579 has an associated T box element, the first reported instance of potential T box control of LysRS expression. Results A global study of 891 completely sequenced bacterial genomes identified T box elements associated with control of LysRS expression in only four bacterial species: B. cereus, B. thuringiensis, Symbiobacterium thermophilum and Clostridium beijerinckii. Here we investigate the T box element found in the regulatory region of the lysK gene in B. cereus strain 14579. We show that this T box element is functional, responding in a canonical manner to an increased level of uncharged tRNALys but, unusually, also responding to an increased level of uncharged tRNAAsn. We also show that B. subtilis strains with T box regulated expression of the endogenous lysS or the heterologous lysK genes are viable. Conclusions The T box element controlling lysK (encoding LysRS1) expression in B. cereus strain 14579 is functional, but unusually responds to depletion of charged tRNALys and tRNAAsn. This may have the advantage of making LysRS1 expression responsive to a wider range of nutritional stresses. The viability of B. subtilis strains with a single LysRS1 or LysRS2, whose expression is controlled by this T box element, makes the rarity of the occurrence of such control of LysRS expression puzzling.

  20. The T box regulatory element controlling expression of the class I lysyl-tRNA synthetase of Bacillus cereus strain 14579 is functional and can be partially induced by reduced charging of asparaginyl-tRNAAsn

    Directory of Open Access Journals (Sweden)

    Conant Gavin C

    2010-07-01

    Full Text Available Abstract Background Lysyl-tRNA synthetase (LysRS is unique within the aminoacyl-tRNA synthetase family in that both class I (LysRS1 and class II (LysRS2 enzymes exist. LysRS1 enzymes are found in Archaebacteria and some eubacteria while all other organisms have LysRS2 enzymes. All sequenced strains of Bacillus cereus (except AH820 and Bacillus thuringiensis however encode both a class I and a class II LysRS. The lysK gene (encoding LysRS1 of B. cereus strain 14579 has an associated T box element, the first reported instance of potential T box control of LysRS expression. Results A global study of 891 completely sequenced bacterial genomes identified T box elements associated with control of LysRS expression in only four bacterial species: B. cereus, B. thuringiensis, Symbiobacterium thermophilum and Clostridium beijerinckii. Here we investigate the T box element found in the regulatory region of the lysK gene in B. cereus strain 14579. We show that this T box element is functional, responding in a canonical manner to an increased level of uncharged tRNALys but, unusually, also responding to an increased level of uncharged tRNAAsn. We also show that B. subtilis strains with T box regulated expression of the endogenous lysS or the heterologous lysK genes are viable. Conclusions The T box element controlling lysK (encoding LysRS1 expression in B. cereus strain 14579 is functional, but unusually responds to depletion of charged tRNALys and tRNAAsn. This may have the advantage of making LysRS1 expression responsive to a wider range of nutritional stresses. The viability of B. subtilis strains with a single LysRS1 or LysRS2, whose expression is controlled by this T box element, makes the rarity of the occurrence of such control of LysRS expression puzzling.

  1. The transcription factor encyclopedia.

    Science.gov (United States)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I; Bolotin, Eugene; Ticoll, Amy; Cheung, Warren A; Zhang, Xiao Yu Cindy; Dickman, Christopher T D; Fulton, Debra L; Lim, Jonathan S; Schnabl, Jake M; Ramos, Oscar H P; Vasseur-Cognet, Mireille; de Leeuw, Charles N; Simpson, Elizabeth M; Ryffel, Gerhart U; Lam, Eric W-F; Kist, Ralf; Wilson, Miranda S C; Marco-Ferreres, Raquel; Brosens, Jan J; Beccari, Leonardo L; Bovolenta, Paola; Benayoun, Bérénice A; Monteiro, Lara J; Schwenen, Helma D C; Grontved, Lars; Wederell, Elizabeth; Mandrup, Susanne; Veitia, Reiner A; Chakravarthy, Harini; Hoodless, Pamela A; Mancarelli, M Michela; Torbett, Bruce E; Banham, Alison H; Reddy, Sekhar P; Cullum, Rebecca L; Liedtke, Michaela; Tschan, Mario P; Vaz, Michelle; Rizzino, Angie; Zannini, Mariastella; Frietze, Seth; Farnham, Peggy J; Eijkelenboom, Astrid; Brown, Philip J; Laperrière, David; Leprince, Dominique; de Cristofaro, Tiziana; Prince, Kelly L; Putker, Marrit; del Peso, Luis; Camenisch, Gieri; Wenger, Roland H; Mikula, Michal; Rozendaal, Marieke; Mader, Sylvie; Ostrowski, Jerzy; Rhodes, Simon J; Van Rechem, Capucine; Boulay, Gaylor; Olechnowicz, Sam W Z; Breslin, Mary B; Lan, Michael S; Nanan, Kyster K; Wegner, Michael; Hou, Juan; Mullen, Rachel D; Colvin, Stephanie C; Noy, Peter John; Webb, Carol F; Witek, Matthew E; Ferrell, Scott; Daniel, Juliet M; Park, Jason; Waldman, Scott A; Peet, Daniel J; Taggart, Michael; Jayaraman, Padma-Sheela; Karrich, Julien J; Blom, Bianca; Vesuna, Farhad; O'Geen, Henriette; Sun, Yunfu; Gronostajski, Richard M; Woodcroft, Mark W; Hough, Margaret R; Chen, Edwin; Europe-Finner, G Nicholas; Karolczak-Bayatti, Magdalena; Bailey, Jarrod; Hankinson, Oliver; Raman, Venu; LeBrun, David P; Biswal, Shyam; Harvey, Christopher J; DeBruyne, Jason P; Hogenesch, John B; Hevner, Robert F; Héligon, Christophe; Luo, Xin M; Blank, Marissa Cathleen; Millen, Kathleen Joyce; Sharlin, David S; Forrest, Douglas; Dahlman-Wright, Karin; Zhao, Chunyan; Mishima, Yuriko; Sinha, Satrajit; Chakrabarti, Rumela; Portales-Casamar, Elodie; Sladek, Frances M; Bradley, Philip H; Wasserman, Wyeth W

    2012-01-01

    Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130 mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written and vetted by experts in the field. TFe is available at http://www.cisreg.ca/tfe.

  2. The Transcription Factor Encyclopedia

    DEFF Research Database (Denmark)

    Yusuf, Dimas; Butland, Stefanie L; Swanson, Magdalena I

    2012-01-01

    mini review articles on pertinent human, mouse and rat TFs. Notable features of the TFe website include a high-quality PDF generator and web API for programmatic data retrieval. TFe aims to rapidly educate scientists about the TFs they encounter through the delivery of succinct summaries written......ABSTRACT: Here we present the Transcription Factor Encyclopedia (TFe), a new web-based compendium of mini review articles on transcription factors (TFs) that is founded on the principles of open access and collaboration. Our consortium of over 100 researchers has collectively contributed over 130...

  3. Multiple sigma subunits and the partitioning of bacterial transcription space.

    Science.gov (United States)

    Gruber, Tanja M; Gross, Carol A

    2003-01-01

    Promoter recognition in eubacteria is carried out by the initiation factor sigma, which binds RNA polymerase and initiates transcription. Cells have one housekeeping factor and a variable number of alternative sigma factors that possess different promoter-recognition properties. The cell can choose from its repertoire of sigmas to alter its transcriptional program in response to stress. Recent structural information illuminates the process of initiation and also shows that the two key sigma domains are structurally conserved, even among diverse family members. We use the sigma repertoire of Escherichia coli, Bacillus subtilis, Streptomyces coelicolor, and cyanobacteria to illustrate the different strategies utilized to organize transcriptional space using multiple sigma factors.

  4. Systematic identification of transcription factors associated with patient survival in cancers

    Directory of Open Access Journals (Sweden)

    Alves Pedro

    2009-05-01

    Full Text Available Abstract Background Aberrant activation or expression of transcription factors has been implicated in the tumorigenesis of various types of cancer. In spite of the prevalent application of microarray experiments for profiling gene expression in cancer samples, they provide limited information regarding the activities of transcription factors. However, the association between transcription factors and cancers is largely dependent on the transcription regulatory activities rather than mRNA expression levels. Results In this paper, we propose a computational approach that integrates microarray expression data with the transcription factor binding site information to systematically identify transcription factors associated with patient survival given a specific cancer type. This approach was applied to two gene expression data sets for breast cancer and acute myeloid leukemia. We found that two transcription factor families, the steroid nuclear receptor family and the ATF/CREB family, are significantly correlated with the survival of patients with breast cancer; and that a transcription factor named T-cell acute lymphocytic leukemia 1 is significantly correlated with acute myeloid leukemia patient survival. Conclusion Our analysis identifies transcription factors associating with patient survival and provides insight into the regulatory mechanism underlying the breast cancer and leukemia. The transcription factors identified by our method are biologically meaningful and consistent with prior knowledge. As an insightful tool, this approach can also be applied to other microarray cancer data sets to help researchers better understand the intricate relationship between transcription factors and diseases.

  5. Rhythm quantization for transcription

    NARCIS (Netherlands)

    Cemgil, A.T.; Desain, P.W.M.; Kappen, H.J.

    1999-01-01

    Automatic Music Transcription is the extraction of an acceptable notation from performed music. One important task in this problem is rhythm quantization which refers to categorization of note durations. Although quantization of a pure mechanical performance is rather straightforward, the task becom

  6. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any a

  7. Mapping yeast transcriptional networks.

    Science.gov (United States)

    Hughes, Timothy R; de Boer, Carl G

    2013-09-01

    The term "transcriptional network" refers to the mechanism(s) that underlies coordinated expression of genes, typically involving transcription factors (TFs) binding to the promoters of multiple genes, and individual genes controlled by multiple TFs. A multitude of studies in the last two decades have aimed to map and characterize transcriptional networks in the yeast Saccharomyces cerevisiae. We review the methodologies and accomplishments of these studies, as well as challenges we now face. For most yeast TFs, data have been collected on their sequence preferences, in vivo promoter occupancy, and gene expression profiles in deletion mutants. These systematic studies have led to the identification of new regulators of numerous cellular functions and shed light on the overall organization of yeast gene regulation. However, many yeast TFs appear to be inactive under standard laboratory growth conditions, and many of the available data were collected using techniques that have since been improved. Perhaps as a consequence, comprehensive and accurate mapping among TF sequence preferences, promoter binding, and gene expression remains an open challenge. We propose that the time is ripe for renewed systematic efforts toward a complete mapping of yeast transcriptional regulatory mechanisms.

  8. Bayesian Music Transcription

    NARCIS (Netherlands)

    Cemgil, A.T.

    2004-01-01

    Music transcription refers to extraction of a human readable and interpretable description from a recording of a music performance. The final goal is to implement a program that can automatically infer a musical notation that lists the pitch levels of notes and corresponding score positions in any

  9. Isl1 is a direct transcriptional target of Forkhead transcription factors in second heart field-derived mesoderm

    Science.gov (United States)

    Kang, Jione; Nathan, Elisha; Xu, Shan-Mei; Tzahor, Eldad; Black, Brian L.

    2009-01-01

    The cells of the second heart field (SHF) contribute to the outflow tract and right ventricle, as well as to parts of the left ventricle and atria. Isl1, a member of the LIM-homeodomain transcription factor family, is expressed early in this cardiac progenitor population and functions near the top of a transcriptional pathway essential for heart development. Isl1 is required for the survival and migration of SHF-derived cells into the early developing heart at the inflow and outflow poles. Despite this important role for Isl1 in early heart formation, the transcriptional regulation of Isl1 has remained largely undefined. Therefore, to identify transcription factors that regulate Isl1 expression in vivo, we screened the conserved noncoding sequences from the mouse Isl1 locus for enhancer activity in transgenic mouse embryos. Here, we report the identification of an enhancer from the mouse Isl1 gene that is sufficient to direct expression to the SHF and its derivatives. The Isl1 SHF enhancer contains three consensus Forkhead transcription factor binding sites that are efficiently and specifically bound by Forkhead transcription factors. Importantly, the activity of the enhancer is dependent on these three Forkhead binding sites in transgenic mouse embryos. Thus, these studies demonstrate that Isl1 is a direct transcriptional target of Forkhead transcription factors in the SHF and establish a transcriptional pathway upstream of Isl1 in the SHF. PMID:19580802

  10. HER4 Cyt1 and Cyt2 Isoforms Regulate Transcription Through Differential Interactions with a Transcriptional Regulator, Yap

    Science.gov (United States)

    2011-10-01

    Smad7[29]. However, the primary target of Yap is thought to be the family of TEF/ TEAD transcription factors, shown by Zhao et al. to be required for...phosphorylation of Yap by HER4 isoforms modulate the ability of Yap to regulate TEF/ TEAD -, RunX2-, and p73-dependent transcription. We will also examine...whether HER4 s80–Cyt1 and –Cyt2 interact with the Yap:transcription factor complex, 11    specifically Yap:TEF/ TEAD , and will evaluate the ability

  11. Transcription Dynamics in Living Cells.

    Science.gov (United States)

    Lenstra, Tineke L; Rodriguez, Joseph; Chen, Huimin; Larson, Daniel R

    2016-07-01

    The transcription cycle can be roughly divided into three stages: initiation, elongation, and termination. Understanding the molecular events that regulate all these stages requires a dynamic view of the underlying processes. The development of techniques to visualize and quantify transcription in single living cells has been essential in revealing the transcription kinetics. They have revealed that (a) transcription is heterogeneous between cells and (b) transcription can be discontinuous within a cell. In this review, we discuss the progress in our quantitative understanding of transcription dynamics in living cells, focusing on all parts of the transcription cycle. We present the techniques allowing for single-cell transcription measurements, review evidence from different organisms, and discuss how these experiments have broadened our mechanistic understanding of transcription regulation.

  12. The EDLL motif: a potent plant transcriptional activation domain from AP2/ERF transcription factors.

    Science.gov (United States)

    Tiwari, Shiv B; Belachew, Alemu; Ma, Siu Fong; Young, Melinda; Ade, Jules; Shen, Yu; Marion, Colleen M; Holtan, Hans E; Bailey, Adina; Stone, Jeffrey K; Edwards, Leslie; Wallace, Andreah D; Canales, Roger D; Adam, Luc; Ratcliffe, Oliver J; Repetti, Peter P

    2012-06-01

    In plants, the ERF/EREBP family of transcriptional regulators plays a key role in adaptation to various biotic and abiotic stresses. These proteins contain a conserved AP2 DNA-binding domain and several uncharacterized motifs. Here, we describe a short motif, termed 'EDLL', that is present in AtERF98/TDR1 and other clade members from the same AP2 sub-family. We show that the EDLL motif, which has a unique arrangement of acidic amino acids and hydrophobic leucines, functions as a strong activation domain. The motif is transferable to other proteins, and is active at both proximal and distal positions of target promoters. As such, the EDLL motif is able to partly overcome the repression conferred by the AtHB2 transcription factor, which contains an ERF-associated amphiphilic repression (EAR) motif. We further examined the activation potential of EDLL by analysis of the regulation of flowering time by NF-Y (nuclear factor Y) proteins. Genetic evidence indicates that NF-Y protein complexes potentiate the action of CONSTANS in regulation of flowering in Arabidopsis; we show that the transcriptional activation function of CONSTANS can be substituted by direct fusion of the EDLL activation motif to NF-YB subunits. The EDLL motif represents a potent plant activation domain that can be used as a tool to confer transcriptional activation potential to heterologous DNA-binding proteins.

  13. TCP transcription factors: architectures of plant form.

    Science.gov (United States)

    Manassero, Nora G Uberti; Viola, Ivana L; Welchen, Elina; Gonzalez, Daniel H

    2013-04-01

    After its initial definition in 1999, the TCP family of transcription factors has become the focus of a multiplicity of studies related with plant development at the cellular, organ, and tissue levels. Evidence has accumulated indicating that TCP transcription factors are the main regulators of plant form and architecture and constitute a tool through which evolution shapes plant diversity. The TCP transcription factors act in a multiplicity of pathways related with cell proliferation and hormone responses. In recent years, the molecular pathways of TCP protein action and biochemical studies on their mode of interaction with DNA have begun to shed light on their mechanism of action. However, the available information is fragmented and a unifying view of TCP protein action is lacking, as well as detailed structural studies of the TCP-DNA complex. Also important, the possible role of TCP proteins as integrators of plant developmental responses to the environment has deserved little attention. In this review, we summarize the current knowledge about the structure and functions of TCP transcription factors and analyze future perspectives for the study of the role of these proteins and their use to modify plant development.

  14. Progress on the role of the signal transducers and activators of transcription family molecules in the regulation of macrophage polarization%信号转导及转录激活因子家族分子在巨噬细胞极化调控中的作用研究进展

    Institute of Scientific and Technical Information of China (English)

    蒋兴伟; 黎燕; 韩根成

    2015-01-01

    Macrophages play a key role in the regulation of inflammation and immune responses,and in the maintenance of immune homeostasis.Under different microenvironments,macrophages function heterogeneously.They can alter themselves into two different types of polarization,classically-activated (M1) and alternatively-activated (M2),in order to display pro-inflammatory or anti-inflammatory functions.Many regulatory molecules are involved in this progress of macrophage polarization.Among these regulatory molecules,signal transducers and activators of transcription (Stats) family is of the most important.Stats family has seven members with similar structures and different functions,called Stat1,Star2,Stat3,Stat4,Stat5a,Stat5b,and Star6.It is clear now that Stats family plays an important role in inflammatory responses,and in the process of macrophage polarization.%巨噬细胞在调控炎症及免疫反应,维持免疫稳态中发挥关键的作用.不同微环境条件下,巨噬细胞功能出现异质性.其可以极化为经典活化(M1)或替代活化(M2)两种不同的极化类型,分别发挥促炎或抑炎的功能.众所周知,许多调控分子参与了巨噬细胞的极化调控过程.在众多的极化调控分子中,信号转导及转录激活因子(Stats)家族是一类最主要的调控分子.Stats家族有7个成员,即Stat1、Stat2、Stat3、Stat4、Stat5a、Stat5b和Stat6.它们结构相似,但功能不同.目前已经明确,Stats分子在机体炎症应答中发挥重要的作用,调控着巨噬细胞的极化进程.

  15. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  16. My Family

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Everyone has a family.We live in it and feel very warm.There are three persons in my family,my mother,father and I.We live together very happily and there are many interesting stories about my family. My father is a hard-working man.He works as a doctor.He always tries his best to help every,patient and make patients comfortable.But sonetimes he works so hard

  17. Family Polymorphism

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    safety and flexibility at the level of multi-object systems. We are granted the flexibility of using different families of kinds of objects, and we are guaranteed the safety of the combination. This paper highlights the inability of traditional polymorphism to handle multiple objects, and presents family...... polymorphism as a way to overcome this problem. Family polymorphism has been implemented in the programming language gbeta, a generalized version of Beta, and the source code of this implementation is available under GPL....

  18. Family literacy

    DEFF Research Database (Denmark)

    Sehested, Caroline

    2012-01-01

    I Projekt familielæsning, der er et samarbejde mellem Nationalt Videncenter for Læsning og Hillerød Bibliotek, arbejder vi med at få kontakt til de familier, som biblioteket ellers aldrig ser som brugere og dermed også de børn, der vokser op i familier, for hvem bøger og oplæsningssituationer ikke...... er en selvfølgelig del af barndommen. Det, vi vil undersøge og ønsker at være med til at udvikle hos disse familier, er det, man kan kalde family literacy....

  19. Non-transcriptional regulatory processes shape transcriptional network dynamics

    OpenAIRE

    Ray, J. Christian J; Tabor, Jeffrey J.; Igoshin, Oleg A.

    2011-01-01

    Information about the extra- or intracellular environment is often captured as biochemical signals propagating through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programs in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. In many cases, the dynamical performance of transcriptional re...

  20. Eukaryotic transcription factors

    DEFF Research Database (Denmark)

    Staby, Lasse; O'Shea, Charlotte; Willemoës, Martin

    2017-01-01

    Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains...... targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID...... them to participate in large interactomes, how they use only a few hydrophobic residues, short sequence motifs, prestructured motifs, and coupled folding and binding for their interactions with co-activators, and how their accessibility to post-translational modification affects their interactions...

  1. DNA Topoisomerases in Transcription

    DEFF Research Database (Denmark)

    Rødgaard, Morten Terpager

    2015-01-01

    This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most of the ex......This Ph.D. thesis summarizes the main results of my studies on the interplay between DNA topoisomerases and transcription. The work was performed from 2011 to 2015 at Aarhus University in the Laboratory of Genome Research, and was supervised by associate professor Anni H. Andersen. Most...... topoisomerase-DNA cleavage complex. The second study is an investigation of how topoisomerases influence gene regulation by keeping the genome in an optimal topological state....

  2. SNFing HIV transcription

    Directory of Open Access Journals (Sweden)

    Bukrinsky Michael

    2006-08-01

    Full Text Available Abstract The SWI/SNF chromatin remodeling complex is an essential regulator of transcription of cellular genes. HIV-1 infection induces exit of a core component of SWI/SNF, Ini1, into the cytoplasm and its association with the viral pre-integration complex. Several recent papers published in EMBO Journal, Journal of Biological Chemistry, and Retrovirology provide new information regarding possible functions of Ini1 and SWI/SNF in HIV life cycle. It appears that Ini1 has an inhibitory effect on pre-integration steps of HIV replication, but also contributes to stimulation of Tat-mediated transcription. This stimulation involves displacement of the nucleosome positioned at the HIV promoter.

  3. Deciphering Transcriptional Regulation

    DEFF Research Database (Denmark)

    Valen, Eivind

    RNA); and ii) translation, in which the mRNA is translated into a protein. This thesis focus on the ¿rst of these steps, transcription, and speci¿cally the initiation of this. Simpli¿ed, initiation is preceded by the binding of several proteins, known as transcription factors (TFs), to DNA. This takes place......The myriad of cells in the human body are all made from the same blueprint: the human genome. At the heart of this diversity lies the concept of gene regulation, the process in which it is decided which genes are used where and when. Genes do not function as on/off buttons, but more like a volume...... control spanning the range from completely muted to cranked up to maximum. The volume, in this case, is the production rate of proteins. This production is the result of a two step procedure: i) transcription, in which a small part of DNA from the genome (a gene) is transcribed into an RNA molecule (an m...

  4. Evolution of transcriptional networks in yeast: alternative teams of transcriptional factors for different species

    Directory of Open Access Journals (Sweden)

    Adriana Muñoz

    2016-11-01

    Full Text Available Abstract Background The diversity in eukaryotic life reflects a diversity in regulatory pathways. Nocedal and Johnson argue that the rewiring of gene regulatory networks is a major force for the diversity of life, that changes in regulation can create new species. Results We have created a method (based on our new “ping-pong algorithm for detecting more complicated rewirings, where several transcription factors can substitute for one or more transcription factors in the regulation of a family of co-regulated genes. An example is illustrative. A rewiring has been reported by Hogues et al. that RAP1 in Saccharomyces cerevisiae substitutes for TBF1/CBF1 in Candida albicans for ribosomal RP genes. There one transcription factor substitutes for another on some collection of genes. Such a substitution is referred to as a “rewiring”. We agree with this finding of rewiring as far as it goes but the situation is more complicated. Many transcription factors can regulate a gene and our algorithm finds that in this example a “team” (or collection of three transcription factors including RAP1 substitutes for TBF1 for 19 genes. The switch occurs for a branch of the phylogenetic tree containing 10 species (including Saccharomyces cerevisiae, while the remaining 13 species (Candida albicans are regulated by TBF1. Conclusions To gain insight into more general evolutionary mechanisms, we have created a mathematical algorithm that finds such general switching events and we prove that it converges. Of course any such computational discovery should be validated in the biological tests. For each branch of the phylogenetic tree and each gene module, our algorithm finds a sub-group of co-regulated genes and a team of transcription factors that substitutes for another team of transcription factors. In most cases the signal will be small but in some cases we find a strong signal of switching. We report our findings for 23 Ascomycota fungi species.

  5. TOBFAC: the database of tobacco transcription factors

    Directory of Open Access Journals (Sweden)

    Brannock Jennifer F

    2008-01-01

    Full Text Available Abstract Background Regulation of gene expression at the level of transcription is a major control point in many biological processes. Transcription factors (TFs can activate and/or repress the transcriptional rate of target genes and vascular plant genomes devote approximately 7% of their coding capacity to TFs. Global analysis of TFs has only been performed for three complete higher plant genomes – Arabidopsis (Arabidopsis thaliana, poplar (Populus trichocarpa and rice (Oryza sativa. Presently, no large-scale analysis of TFs has been made from a member of the Solanaceae, one of the most important families of vascular plants. To fill this void, we have analysed tobacco (Nicotiana tabacum TFs using a dataset of 1,159,022 gene-space sequence reads (GSRs obtained by methylation filtering of the tobacco genome. An analytical pipeline was developed to isolate TF sequences from the GSR data set. This involved multiple (typically 10–15 independent searches with different versions of the TF family-defining domain(s (normally the DNA-binding domain followed by assembly into contigs and verification. Our analysis revealed that tobacco contains a minimum of 2,513 TFs representing all of the 64 well-characterised plant TF families. The number of TFs in tobacco is higher than previously reported for Arabidopsis and rice. Results TOBFAC: the database of tobacco transcription factors, is an integrative database that provides a portal to sequence and phylogeny data for the identified TFs, together with a large quantity of other data concerning TFs in tobacco. The database contains an individual page dedicated to each of the 64 TF families. These contain background information, domain architecture via Pfam links, a list of all sequences and an assessment of the minimum number of TFs in this family in tobacco. Downloadable phylogenetic trees of the major families are provided along with detailed information on the bioinformatic pipeline that was used to find

  6. Non-transcriptional regulatory processes shape transcriptional network dynamics.

    Science.gov (United States)

    Ray, J Christian J; Tabor, Jeffrey J; Igoshin, Oleg A

    2011-10-11

    Information about the extra- or intracellular environment is often captured as biochemical signals that propagate through regulatory networks. These signals eventually drive phenotypic changes, typically by altering gene expression programmes in the cell. Reconstruction of transcriptional regulatory networks has given a compelling picture of bacterial physiology, but transcriptional network maps alone often fail to describe phenotypes. Cellular response dynamics are ultimately determined by interactions between transcriptional and non-transcriptional networks, with dramatic implications for physiology and evolution. Here, we provide an overview of non-transcriptional interactions that can affect the performance of natural and synthetic bacterial regulatory networks.

  7. Expression of Drosophila forkhead transcription factors during kidney development.

    Science.gov (United States)

    Baek, Jeong-In; Choi, Soo Young; Chacon-Heszele, Maria F; Zuo, Xiaofeng; Lipschutz, Joshua H

    2014-03-28

    The Drosophila forkhead (Dfkh) family of transcription factors has over 40 family members. One Dfkh family member, BF2 (aka FoxD1), has been shown, by targeted disruption, to be essential for kidney development. In order to determine if other Dfkh family members were involved in kidney development and to search for new members of this family, reverse transcriptase polymerase chain reaction (RT-PCR) was performed using degenerate primers of the consensus sequence of the DNA binding domain of this family and developing rat kidney RNA. The RT-PCR product was used to probe RNA from a developing rat kidney (neonatal), from a 20-day old kidney, and from an adult kidney. The RT-PCR product hybridized only to a developing kidney RNA transcript of ∼2.3 kb (the size of BF2). A lambda gt10 mouse neonatal kidney library was then screened, using the above-described RT-PCR product as a probe. Three lambda phage clones were isolated that strongly hybridized to the RT-PCR probe. Sequencing of the RT-PCR product and the lambda phage clones isolated from the developing kidney library revealed Dfkh BF2. In summary, only Dfkh family member BF2, which has already been shown to be essential for nephrogenesis, was identified in our screen and no other candidate Dfkh family members were identified.

  8. Small Families

    Science.gov (United States)

    ... easier for both parents to combine careers with family life. The general stress level is lower because there often are fewer ... can help replace the missing ties. For many families, religious congregational ... such as youth and neighborhood activity centers also can fulfill these ...

  9. FAMILY PLATYSTOMATIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli

    2016-06-14

    Platystomatidae (Signal Flies) are one of the largest families of Tephritoidea, with about 1200 species and four subfamilies, worldwide distributed. However, Platystomatidae are not well represented in the New World, and in the Neotropical Region only four genera and 26 species, belonging to Platystomatinae, are recorded. The family is a group understudied in Colombia and only one species is recorded to the country.

  10. Analysis of tomato spotted wilt virus genome transcription

    NARCIS (Netherlands)

    Knippenberg, van I.C.

    2005-01-01

    Tomato spotted wilt virus (TSWV) is the type species of the genus Tospovirus within the Bunyaviridae, a family of segmented negative strand RNA viruses. Although much ground has been covered in the past two decades, many questions concerning the mechanism of replication and transcription of this

  11. Analysis of tomato spotted wilt virus genome transcription

    NARCIS (Netherlands)

    Knippenberg, van I.C.

    2005-01-01

    Tomato spotted wilt virus (TSWV) is the type species of the genus Tospovirus within the Bunyaviridae, a family of segmented negative strand RNA viruses. Although much ground has been covered in the past two decades, many questions concerning the mechanism of replication and transcription of this imp

  12. New insight into transcription of human endogenous retroviral elements.

    Science.gov (United States)

    Pačes, Jan; Huang, Yao-Ting; Pačes, Václav; Rídl, Jakub; Chang, Chung-Ming

    2013-03-25

    It is generally assumed that human endogenous retroviral elements (HERVs) belong to the class of genomic repetitive nucleotide sequences often called 'junk DNA'. These elements were categorized to families, and members of some of these families (e.g. HERV-H, HERV-W and HERV-K) were shown to be transcribed. These transcriptions were associated with several severe diseases such as mental disorders, AIDS, autoimmune diseases and cancer. In this review we discuss several bioinformatics strategies for genome-wide scan of HERVs transcription using high-throughput RNA sequencing on several platforms. We show that many more HERVs than previously described are transcribed to various levels and we discuss possible implications of these transcriptions.

  13. To Your Health: NLM update transcript - Family health portrait

    Science.gov (United States)

    ... Regards to all our listeners! I'm Rob Logan, Ph.D., senior staff, U.S. National Library of ... care provider — regardless if you are strangers or old friends. The reason is many common diseases, such ...

  14. The zebrafish progranulin gene family and antisense transcripts

    Directory of Open Access Journals (Sweden)

    Baranowski David

    2005-11-01

    Full Text Available Abstract Background Progranulin is an epithelial tissue growth factor (also known as proepithelin, acrogranin and PC-cell-derived growth factor that has been implicated in development, wound healing and in the progression of many cancers. The single mammalian progranulin gene encodes a glycoprotein precursor consisting of seven and one half tandemly repeated non-identical copies of the cystine-rich granulin motif. A genome-wide duplication event hypothesized to have occurred at the base of the teleost radiation predicts that mammalian progranulin may be represented by two co-orthologues in zebrafish. Results The cDNAs encoding two zebrafish granulin precursors, progranulins-A and -B, were characterized and found to contain 10 and 9 copies of the granulin motif respectively. The cDNAs and genes encoding the two forms of granulin, progranulins-1 and -2, were also cloned and sequenced. Both latter peptides were found to be encoded by precursors with a simplified architecture consisting of one and one half copies of the granulin motif. A cDNA encoding a chimeric progranulin which likely arises through the mechanism of trans-splicing between grn1 and grn2 was also characterized. A non-coding RNA gene with antisense complementarity to both grn1 and grn2 was identified which may have functional implications with respect to gene dosage, as well as in restricting the formation of the chimeric form of progranulin. Chromosomal localization of the four progranulin (grn genes reveals syntenic conservation for grna only, suggesting that it is the true orthologue of mammalian grn. RT-PCR and whole-mount in situ hybridization analysis of zebrafish grns during development reveals that combined expression of grna and grnb, but not grn1 and grn2, recapitulate many of the expression patterns observed for the murine counterpart. This includes maternal deposition, widespread central nervous system distribution and specific localization within the epithelial compartments of various organs. Conclusion In support of the duplication-degeneration-complementation model of duplicate gene retention, partitioning of expression between grna and grnb was observed in the intermediate cell mass and yolk syncytial layer, respectively. Taken together these expression patterns suggest that the function of an ancestral grn gene has been devolved upon four paralogues in zebrafish.

  15. The bZip transcription factor vitellogenin-binding protein is post transcriptional down regulated in chicken liver

    NARCIS (Netherlands)

    Smidt, MP; Snippe, L; Van Keulen, G; Ab, G

    1998-01-01

    The vitellogenin-binding protein (VBP) is a member of the proline and acidic-region rich (PAR) family of bZip transcription factors. PAR is located N-terminally to the DNA-binding domain. VBP binds to specific sites within the 300-bp 5'-flanking region of the chicken-liver-specific estrogen-dependen

  16. AKNA: Another AT-hook transcription factor"hooking-up"with inflammation

    Institute of Scientific and Technical Information of China (English)

    Alison R Moliterno; Linda MS Resar

    2011-01-01

    Previous studies highlight a key role for AT-hook transcription factors as master regulators of fundamental cellular processes involved in development,immune function,cancer,diabetes and other human diseases [1,2].The high mobility group A (HMGA) proteins are an important family of AT-hook chromatin remodeling proteins that orchestrate transcriptional complexes to regulate gene expression [ 1 ].Recent studies have uncovered links between HMG AT-hook transcription factors and inflammation [1-8].

  17. Effects of downregulating TEAD4 transcripts by RNA interference on early development of bovine embryos

    OpenAIRE

    SAKURAI, Nobuyuki; Takahashi, Kazuki; EMURA, Natsuko; HASHIZUME, Tsutomu; SAWAI, Ken

    2016-01-01

    Transcription factor TEA domain family transcription factor 4 (Tead4) is one of the key factors involved in the differentiation of the trophectoderm (TE) in murine embryos. However, knowledge on the roles of TEAD4 in preimplantation development during bovine embryos is currently limited. This study examined the transcript and protein expression patterns of TEAD4 and attempted to elucidate the functions of TEAD4 during bovine preimplantation development using RNA interference. TEAD4 mRNA was f...

  18. Initiation and regulation of paramyxovirus transcription and replication.

    Science.gov (United States)

    Noton, Sarah L; Fearns, Rachel

    2015-05-01

    The paramyxovirus family has a genome consisting of a single strand of negative sense RNA. This genome acts as a template for two distinct processes: transcription to generate subgenomic, capped and polyadenylated mRNAs, and genome replication. These viruses only encode one polymerase. Thus, an intriguing question is, how does the viral polymerase initiate and become committed to either transcription or replication? By answering this we can begin to understand how these two processes are regulated. In this review article, we present recent findings from studies on the paramyxovirus, respiratory syncytial virus, which show how its polymerase is able to initiate transcription and replication from a single promoter. We discuss how these findings apply to other paramyxoviruses. Then, we examine how trans-acting proteins and promoter secondary structure might serve to regulate transcription and replication during different phases of the paramyxovirus replication cycle.

  19. Regulation of the Hippo Pathway Transcription Factor TEAD.

    Science.gov (United States)

    Lin, Kimberly C; Park, Hyun Woo; Guan, Kun-Liang

    2017-09-27

    The TEAD transcription factor family is best known for transcriptional output of the Hippo signaling pathway and has been implicated in processes such as development, cell growth and proliferation, tissue homeostasis, and regeneration. Our understanding of the functional importance of TEADs has increased dramatically since its initial discovery three decades ago. The majority of our knowledge of TEADs is in the context of Hippo signaling as nuclear DNA-binding proteins passively activated by Yes-associated protein (YAP) and transcriptional activator with PDZ-binding domain (TAZ), transcription coactivators downstream of the Hippo pathway. However, recent studies suggest that TEAD itself is actively regulated. Here, we highlight evidence demonstrating Hippo-independent regulation of TEADs and the potential impacts these studies may have on new cancer therapeutics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. MADS interactomics : towards understanding the molecular mechanisms of plant MADS-domain transcription factor function

    NARCIS (Netherlands)

    Smaczniak, C.D.

    2013-01-01

    Protein-protein and protein-DNA interactions are essential for the molecular action of transcription factors. By combinatorial binding to target gene promoters, transcription factors are able to up- or down-regulate the expression of these genes. MADS-domain proteins comprise a large family of trans

  1. Wnt-induced transcriptional activation is exclusively mediated by TCF/LEF

    NARCIS (Netherlands)

    Schuijers, Jurian; Mokry, Michal; Hatzis, Pantelis; Cuppen, Edwin; Clevers, Hans

    2014-01-01

    Active canonical Wnt signaling results in recruitment of β-catenin to DNA by TCF/LEF family members, leading to transcriptional activation of TCF target genes. However, additional transcription factors have been suggested to recruit β-catenin and tether it to DNA. Here, we describe the genome-wide p

  2. MADS interactomics : towards understanding the molecular mechanisms of plant MADS-domain transcription factor function

    NARCIS (Netherlands)

    Smaczniak, C.D.

    2013-01-01

    Protein-protein and protein-DNA interactions are essential for the molecular action of transcription factors. By combinatorial binding to target gene promoters, transcription factors are able to up- or down-regulate the expression of these genes. MADS-domain proteins comprise a large family of trans

  3. Genomic structure and cloning of two transcript isoforms of human Sp8.

    NARCIS (Netherlands)

    M.A. Milona (Maria-athina); J.E. Gough (Julie); A.J. Edgar (Alasdair)

    2004-01-01

    textabstractBACKGROUND: The Specificity proteins (Sp) are a family of transcription factors that have three highly conserved zinc-fingers located towards the carboxy-terminal that bind GC-boxes and assist in the initiation of gene transcription. Human Sp1-7 genes have been characte

  4. Family Disruptions

    Science.gov (United States)

    ... stay angry, or avoid fights altogether? Your children model themselves on you. Departures and Returns Do you or your spouse frequently travel on business? These can be disruptive times for your child and for the family ...

  5. Familial hypercholesterolemia

    Science.gov (United States)

    ... hypercholesterolemia or early heart attacks High level of LDL cholesterol in either or both parents People from families ... called fibroblasts to see how the body absorbs LDL cholesterol Genetic test for the defect associated with this ...

  6. Family matters

    DEFF Research Database (Denmark)

    Kieffer-Kristensen, Rikke; Siersma, Volkert Dirk; Teasdale, Thomas William

    2013-01-01

    OBJECTIVES: To relate illness and family factors to emotional and behavioural problems in school-age children (7–14 years old) of parents with acquired brain injury and their healthy spouses. PARTICIPANTS, MATERIALS/METHODS: Members of 35 families in which a parent had been diagnosed with acquired...... brain injury participated. Family and brain injury characteristics were reported by the ill and healthy parents. Children self-reported post-traumatic stress symptoms (PSS) using the Child Impact of Events revised (CRIES). Emotional and behavioural problems among the children were also identified...... by the parents using the Achenbach’s Child Behaviour Checklist (CBCL). RESULTS: The family stress variables relating to the healthy spouse in all six comparisons were significant (p

  7. Regulated assembly of transcription factors and control of transcription initiation.

    Science.gov (United States)

    Beckett, D

    2001-11-30

    Proteins that function in regulation of transcription initiation are typically homo or hetero-oligomeric. Results of recent biophysical studies of transcription regulators indicate that the assembly of these proteins is often subject to regulation. This regulation of assembly dictates the frequency of transcription initiation via its influence on the affinity of a transcription regulator for DNA and its affect on target site selection. Factors that modulate transcription factor assembly include binding of small molecules, post-translational modification, DNA binding and interactions with other proteins. Here, the results of recent structural and/or thermodynamic studies of a number of transcription regulators that are subject to regulated assembly are reviewed. The accumulated data indicate that this phenomenon is ubiquitous and that mechanisms utilized in eukaryotes and prokaryotes share common features. Copyright 2001 Academic Press.

  8. Transcriptional analysis of Pleurotus ostreatus laccase genes.

    Science.gov (United States)

    Pezzella, Cinzia; Lettera, Vincenzo; Piscitelli, Alessandra; Giardina, Paola; Sannia, Giovanni

    2013-01-01

    Fungal laccases (p-diphenol:oxygen oxidoreductase; EC 1.10.3.2) are multi-copper-containing oxidases that catalyse the oxidation of a great variety of phenolic compounds and aromatic amines through simultaneous reduction of molecular oxygen to water. Fungi generally produce several laccase isoenzymes encoded by complex multi-gene families. The Pleurotus ostreatus genome encodes 11 putative laccase coding genes, and only six different laccase isoenzymes have been isolated and characterised so far. Laccase expression was found to be regulated by culture conditions and developmental stages even if the redundancy of these genes still raises the question about their respective functions in vivo. In this context, laccase transcript profiling analysis has been used to unravel the physiological role played by the different isoforms produced by P. ostreatus. Even if reported results depict a complex picture of the transcriptional responses exhibited by the analysed laccase genes, they were allowed to speculate on the isoform role in vivo. Among the produced laccases, LACC10 (POXC) seems to play a major role during vegetative growth, since its transcription is downregulated when the fungus starts the fructification process. Furthermore, a new tessera has been added to the puzzling mosaic of the heterodimeric laccase LACC2 (POXA3). LACC2 small subunit seems to play an additional physiological role during fructification, beside that of LACC2 complex activation/stabilisation.

  9. Global analysis of photosynthesis transcriptional regulatory networks.

    Science.gov (United States)

    Imam, Saheed; Noguera, Daniel R; Donohue, Timothy J

    2014-12-01

    Photosynthesis is a crucial biological process that depends on the interplay of many components. This work analyzed the gene targets for 4 transcription factors: FnrL, PrrA, CrpK and MppG (RSP_2888), which are known or predicted to control photosynthesis in Rhodobacter sphaeroides. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) identified 52 operons under direct control of FnrL, illustrating its regulatory role in photosynthesis, iron homeostasis, nitrogen metabolism and regulation of sRNA synthesis. Using global gene expression analysis combined with ChIP-seq, we mapped the regulons of PrrA, CrpK and MppG. PrrA regulates ∼34 operons encoding mainly photosynthesis and electron transport functions, while CrpK, a previously uncharacterized Crp-family protein, regulates genes involved in photosynthesis and maintenance of iron homeostasis. Furthermore, CrpK and FnrL share similar DNA binding determinants, possibly explaining our observation of the ability of CrpK to partially compensate for the growth defects of a ΔFnrL mutant. We show that the Rrf2 family protein, MppG, plays an important role in photopigment biosynthesis, as part of an incoherent feed-forward loop with PrrA. Our results reveal a previously unrealized, high degree of combinatorial regulation of photosynthetic genes and significant cross-talk between their transcriptional regulators, while illustrating previously unidentified links between photosynthesis and the maintenance of iron homeostasis.

  10. Families in the Military

    Science.gov (United States)

    ... Contents Facts For Families Guide - View by Topic Chinese Facts for Families Guide Facts For Families Guide - Search Spanish Facts for Families Guide Facts for Families - Vietnamese Military Families No. 88; updated March 2017 Global conflict ...

  11. Functional and transcriptome analysis reveals an acclimatization strategy for abiotic stress tolerance mediated by Arabidopsis NF-YA family members

    National Research Council Canada - National Science Library

    Leyva-González, Marco Antonio; Ibarra-Laclette, Enrique; Cruz-Ramírez, Alfredo; Herrera-Estrella, Luis

    2012-01-01

    .... Here we report that five members of the Arabidopsis thaliana NF-YA family are strongly induced by several stress conditions via transcriptional and miR169-related post-transcriptional mechanisms...

  12. Two recently duplicated maize NAC transcription factor paralogs are induced in response to Colletotrichum graminicola infection.

    Science.gov (United States)

    Voitsik, Anna-Maria; Muench, Steffen; Deising, Holger B; Voll, Lars M

    2013-05-29

    NAC transcription factors belong to a large family of plant-specific transcription factors with more than 100 family members in monocot and dicot species. To date, the majority of the studied NAC proteins are involved in the response to abiotic stress, to biotic stress and in the regulation of developmental processes. Maize NAC transcription factors involved in the biotic stress response have not yet been identified. We have found that two NAC transcription factors, ZmNAC41 and ZmNAC100, are transcriptionally induced both during the initial biotrophic as well as the ensuing necrotrophic colonization of maize leaves by the hemibiotrophic ascomycete fungus C. graminicola. ZmNAC41 transcripts were also induced upon infection with C. graminicola mutants that are defective in host penetration, while the induction of ZmNAC100 did not occur in such interactions. While ZmNAC41 transcripts accumulated specifically in response to jasmonate (JA), ZmNAC100 transcripts were also induced by the salicylic acid analog 2,6-dichloroisonicotinic acid (INA).To assess the phylogenetic relation of ZmNAC41 and ZmNAC100, we studied the family of maize NAC transcription factors based on the recently annotated B73 genome information. We identified 116 maize NAC transcription factor genes that clustered into 12 clades. ZmNAC41 and ZmNAC100 both belong to clade G and appear to have arisen by a recent gene duplication event. Including four other defence-related NAC transcription factors of maize and functionally characterized Arabidopsis and rice NAC transcription factors, we observed an enrichment of NAC transcription factors involved in host defense regulation in clade G. In silico analyses identified putative binding elements for the defence-induced ERF, Myc2, TGA and WRKY transcription factors in the promoters of four out of the six defence-related maize NAC transcription factors, while one of the analysed maize NAC did not contain any of these potential binding sites. Our study provides a

  13. Transcriptional Silencing of Retroviral Vectors

    DEFF Research Database (Denmark)

    Lund, Anders Henrik; Duch, M.; Pedersen, F.S.

    1996-01-01

    . Extinction of long-term vector expression has been observed after implantation of transduced hematopoietic cells as well as fibroblasts, myoblasts and hepatocytes. Here we review the influence of vector structure, integration site and cell type on transcriptional silencing. While down-regulation of proviral...... transcription is known from a number of cellular and animal models, major insight has been gained from studies in the germ line and embryonal cells of the mouse. Key elements for the transfer and expression of retroviral vectors, such as the viral transcriptional enhancer and the binding site for the t......RNA primer for reverse transcription may have a major influence on transcriptional silencing. Alterations of these elements of the vector backbone as well as the use of internal promoter elements from housekeeping genes may contribute to reduce transcriptional silencing. The use of cell culture and animal...

  14. DNA topology and transcription

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions. PMID:24755522

  15. DNA topology and transcription.

    Science.gov (United States)

    Kouzine, Fedor; Levens, David; Baranello, Laura

    2014-01-01

    Chromatin is a complex assembly that compacts DNA inside the nucleus while providing the necessary level of accessibility to regulatory factors conscripted by cellular signaling systems. In this superstructure, DNA is the subject of mechanical forces applied by variety of molecular motors. Rather than being a rigid stick, DNA possesses dynamic structural variability that could be harnessed during critical steps of genome functioning. The strong relationship between DNA structure and key genomic processes necessitates the study of physical constrains acting on the double helix. Here we provide insight into the source, dynamics, and biology of DNA topological domains in the eukaryotic cells and summarize their possible involvement in gene transcription. We emphasize recent studies that might inspire and impact future experiments on the involvement of DNA topology in cellular functions.

  16. The post-transcriptional operon

    DEFF Research Database (Denmark)

    Tenenbaum, Scott A.; Christiansen, Jan; Nielsen, Henrik

    2011-01-01

    A post-transcriptional operon is a set of monocistronic mRNAs encoding functionally related proteins that are co-regulated by a group of RNA-binding proteins and/or small non-coding RNAs so that protein expression is coordinated at the post-transcriptional level. The post-transcriptional operon...... model (PTO) is used to describe data from an assortment of methods (e.g. RIP-Chip, CLIP-Chip, miRNA profiling, ribosome profiling) that globally address the functionality of mRNA. Several examples of post-transcriptional operons have been documented in the literature and demonstrate the usefulness...

  17. Promoter-mediated transcriptional dynamics.

    Science.gov (United States)

    Zhang, Jiajun; Zhou, Tianshou

    2014-01-21

    Genes in eukaryotic cells are typically regulated by complex promoters containing multiple binding sites for a variety of transcription factors, but how promoter dynamics affect transcriptional dynamics has remained poorly understood. In this study, we analyze gene models at the transcriptional regulation level, which incorporate the complexity of promoter structure (PS) defined as transcriptional exits (i.e., ON states of the promoter) and the transition pattern (described by a matrix consisting of transition rates among promoter activity states). We show that multiple exits of transcription are the essential origin of generating multimodal distributions of mRNA, but promoters with the same transition pattern can lead to multimodality of different modes, depending on the regulation of transcriptional factors. In turn, for similar mRNA distributions in the models, the mean ON or OFF time distributions may exhibit different characteristics, thus providing the supplemental information on PS. In addition, we demonstrate that the transcriptional noise can be characterized by a nonlinear function of mean ON and OFF times. These results not only reveal essential characteristics of promoter-mediated transcriptional dynamics but also provide signatures useful for inferring PS based on characteristics of transcriptional outputs. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  18. Codependent activators direct myoblast-specific MyoD transcription.

    Science.gov (United States)

    Hu, Ping; Geles, Kenneth G; Paik, Ji-Hye; DePinho, Ronald A; Tjian, Robert

    2008-10-01

    Although FoxO and Pax proteins represent two important families of transcription factors in determining cell fate, they had not been functionally or physically linked together in mediating regulation of a common target gene during normal cellular transcription programs. Here, we identify MyoD, a key regulator of myogenesis, as a direct target of FoxO3 and Pax3/7 in myoblasts. Our cell-based assays and in vitro studies reveal a tight codependent partnership between FoxO3 and Pax3/7 to coordinately recruit RNA polymerase II and form a preinitiation complex (PIC) to activate MyoD transcription in myoblasts. The role of FoxO3 in regulating muscle differentiation is confirmed in vivo by observed defects in muscle regeneration caused by MyoD downregulation in FoxO3 null mice. These data establish a mutual interdependence and functional link between two families of transcription activators serving as potential signaling sensors and regulators of cell fate commitment in directing tissue specific MyoD transcription.

  19. Family Literacy

    Directory of Open Access Journals (Sweden)

    Livija Knaflič

    1999-12-01

    Full Text Available Research in child and adult literacy demonstrates that the achievement and the level of literacy that children attain at school is connected with the social and cultural characteristics and the level of literacy of the child's family. This intergenerational transfer of the level of literacy has motivated the search for different ways of improving the level of literacy.The concept of family literacy is based on the assumption that a higher level of parent literacy means that the children may achieve the same, and it also offers better schooling prospects. Family literacy programmes help fami­lies to develop different activities, in­cluding reading and writing skills, both in their community and in everyday life.

  20. Mastering Transcription: Multiplexed Analysis of Transcription Start Site Sequences.

    Science.gov (United States)

    Hochschild, Ann

    2015-12-17

    In this issue of Molecular Cell, Vvedenskaya et al. (2015) describe a high-throughput sequencing-based methodology for the massively parallel analysis of transcription from a high-complexity barcoded template library both in vitro and in vivo, providing a powerful new tool for the study of transcription.

  1. PlnTFDB: an integrative plant transcription factor database

    Directory of Open Access Journals (Sweden)

    Ruzicic Slobodan

    2007-02-01

    Full Text Available Abstract Background Transcription factors (TFs are key regulatory proteins that enhance or repress the transcriptional rate of their target genes by binding to specific promoter regions (i.e. cis-acting elements upon activation or de-activation of upstream signaling cascades. TFs thus constitute master control elements of dynamic transcriptional networks. TFs have fundamental roles in almost all biological processes (development, growth and response to environmental factors and it is assumed that they play immensely important functions in the evolution of species. In plants, TFs have been employed to manipulate various types of metabolic, developmental and stress response pathways. Cross-species comparison and identification of regulatory modules and hence TFs is thought to become increasingly important for the rational design of new plant biomass. Up to now, however, no computational repository is available that provides access to the largely complete sets of transcription factors of sequenced plant genomes. Description PlnTFDB is an integrative plant transcription factor database that provides a web interface to access large (close to complete sets of transcription factors of several plant species, currently encompassing Arabidopsis thaliana (thale cress, Populus trichocarpa (poplar, Oryza sativa (rice, Chlamydomonas reinhardtii and Ostreococcus tauri. It also provides an access point to its daughter databases of a species-centered representation of transcription factors (OstreoTFDB, ChlamyTFDB, ArabTFDB, PoplarTFDB and RiceTFDB. Information including protein sequences, coding regions, genomic sequences, expressed sequence tags (ESTs, domain architecture and scientific literature is provided for each family. Conclusion We have created lists of putatively complete sets of transcription factors and other transcriptional regulators for five plant genomes. They are publicly available through http://plntfdb.bio.uni-potsdam.de. Further data will be

  2. Family Structure and Family Processes in Mexican American Families

    OpenAIRE

    Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

    2011-01-01

    Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct,...

  3. Transcriptional and post-transcriptional profile of human chromosome 21.

    Science.gov (United States)

    Nikolaev, Sergey I; Deutsch, Samuel; Genolet, Raphael; Borel, Christelle; Parand, Leila; Ucla, Catherine; Schütz, Frederic; Duriaux Sail, Genevieve; Dupré, Yann; Jaquier-Gubler, Pascale; Araud, Tanguy; Conne, Beatrice; Descombes, Patrick; Vassalli, Jean-Dominique; Curran, Joseph; Antonarakis, Stylianos E

    2009-08-01

    Recent studies have demonstrated extensive transcriptional activity across the human genome, a substantial fraction of which is not associated with any functional annotation. However, very little is known regarding the post-transcriptional processes that operate within the different classes of RNA molecules. To characterize the post-transcriptional properties of expressed sequences from human chromosome 21 (HSA21), we separated RNA molecules from three cell lines (GM06990, HeLa S3, and SK-N-AS) according to their ribosome content by sucrose gradient fractionation. Polyribosomal-associated RNA and total RNA were subsequently hybridized to genomic tiling arrays. We found that approximately 50% of the transcriptional signals were located outside of annotated exons and were considered as TARs (transcriptionally active regions). Although TARs were observed among polysome-associated RNAs, RT-PCR and RACE experiments revealed that approximately 40% were likely to represent nonspecific cross-hybridization artifacts. Bioinformatics discrimination of TARs according to conservation and sequence complexity allowed us to identify a set of high-confidence TARs. This set of TARs was significantly depleted in the polysomes, suggesting that it was not likely to be involved in translation. Analysis of polysome representation of RefSeq exons showed that at least 15% of RefSeq transcripts undergo significant post-transcriptional regulation in at least two of the three cell lines tested. Among the regulated transcripts, enrichment analysis revealed an over-representation of genes involved in Alzheimer's disease (AD), including APP and the BACE1 protease that cleaves APP to produce the pathogenic beta 42 peptide. We demonstrate that the combination of RNA fractionation and tiling arrays is a powerful method to assess the transcriptional and post-transcriptional properties of genomic regions.

  4. Family Circle

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Foster care is conducive to giving orphaned children a better life For most children living in orphanages, having a real home is just a pipe dream. Although they may be well looked after, receive a good education and proper nutrition, the love and care that come from being part of a real family just aren't there.

  5. My Family

    Institute of Scientific and Technical Information of China (English)

    刘才来

    2002-01-01

    There are four people in my family. They are grandma, father,mother and I. Now we all live in Wuhan. They are from different places. My grandma comes from Sichuan. She likes hot(辣4的) meat very much. She doesn't like bread or noodles at all. She likes vegetables a little. My father is from Guang Zhou.

  6. My Family

    Institute of Scientific and Technical Information of China (English)

    李梅

    2012-01-01

    There are four people in my family--my parents, my brother and I. My name is Li Mei. I'm fifteen years old. I am of medium height and build. I like English very much. It's very interesting. I can play the piano very well. It makes me feel very happy.

  7. Finding Family

    Institute of Scientific and Technical Information of China (English)

    LIU YUNYUN

    2010-01-01

    @@ It took 14 years--and just two min-utes-for an adopted Chinese girl to find her biological family. July 21 this year marked the first anniversary of Haley Butler's finding of her biological parents in Maanshan in east China's Anhui Province.

  8. FAMILY RICHARDIIDAE.

    Science.gov (United States)

    Wendt, Lisiane Dilli; Ale-Rocha, Rosaly

    2016-06-14

    Richardiidae are a family of "acalyptrate" Diptera represented by ca. 180 species distributed in the New World, mostly in the Neotropical region. The species that occur in Colombia have received little attention from taxonomists, and the great majority of them are known only from their type localities. Currently, 14 genera and 23 species are known to occur in the country.

  9. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  10. Finding Family

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Discovering her birth parents was an exciting adventure for a 15-year-old girl It took 14 years-and just two minutes-for an adopted Chinese girl to find her biological family.July 21 this year marked the first

  11. Familial hypercholesterolaemia

    DEFF Research Database (Denmark)

    Versmissen, Jorie; Vongpromek, Ranitha; Yahya, Reyhana

    2016-01-01

    cholesterol efflux capacity between male familial hypercholesterolaemia (FH) patients with and without CHD relative to their non-FH brothers, and examined HDL constituents including sphingosine-1-phosphate (S1P) and its carrier apolipoprotein M (apoM). RESULTS: Seven FH patients were asymptomatic and six had...

  12. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  13. [Transcription Factors in Developmental Genetics and the Evolution of Higher Plants].

    Science.gov (United States)

    Lutova, L A; Dodueva, I E; Lebedeva, M A; Tvorogova, V E

    2015-05-01

    Transcription factors play an essential role in controlling various developmental programs in plants, coordinating the action of any genetic network. Among the most important groups of plant transcription factors are the homeodomain-containing transcription factors, in particular, those belonging to the KNOX and WOX families, the functions of which are associated with regulation of the meristem activity, development of the aboveground and underground parts of plants, and control of embryogenesis. This review examines the role of KNOX and WOX transcription factors in various developmental programs, as well as in the evolutionary complication of the body plan in terrestrial plants.

  14. The Role of the TEF Transcription Factors in Cardiogenesis and Other Developmental Processes.

    Science.gov (United States)

    Jacquemin, P; Davidson, I

    1997-08-01

    The development of complex tissues and organs during embryogenesis is accompanied by precise spatial and temporal gene regulation, which usually takes place at the level of transcription initiation by RNA polymerase II. Differential patterns of gene expression are controlled by the binding of combinatorial arrays of transcription factors to their cognate regulatory elements in the promoters and enhancers of target genes. Generally, these transcription factors belong to families that have arisen through gene duplication. Members of a given family can be identified by the fact that they possess a common DNA-binding domain. In this review, we present the current data arguing for the possible involvement of the TEF family of transcription factors, which contain the TEA DNA-binding domain, in cardiogenesis and in other developmental processes. (Trends Cardiovasc Med 1997;7:192-197). © 1997, Elsevier Science Inc.

  15. DNA-binding specificity and molecular functions of NAC transcription factors

    DEFF Research Database (Denmark)

    Olsen, Addie Nina; Ernst, Heidi Asschenfeldt; Lo Leggio, Leila;

    2005-01-01

    The family of NAC (NAM/ATAF1,2/CUC2) transcription factors has been implicated in a wide range of plant processes, but knowledge on the DNA-binding properties of the family is limited. Using a reiterative selection procedure on random oligonucleotides, we have identified consensus binding sites f...

  16. Mechanosensitive mechanisms in transcriptional regulation.

    Science.gov (United States)

    Mammoto, Akiko; Mammoto, Tadanori; Ingber, Donald E

    2012-07-01

    Transcriptional regulation contributes to the maintenance of pluripotency, self-renewal and differentiation in embryonic cells and in stem cells. Therefore, control of gene expression at the level of transcription is crucial for embryonic development, as well as for organogenesis, functional adaptation, and regeneration in adult tissues and organs. In the past, most work has focused on how transcriptional regulation results from the complex interplay between chemical cues, adhesion signals, transcription factors and their co-regulators during development. However, chemical signaling alone is not sufficient to explain how three-dimensional (3D) tissues and organs are constructed and maintained through the spatiotemporal control of transcriptional activities. Accumulated evidence indicates that mechanical cues, which include physical forces (e.g. tension, compression or shear stress), alterations in extracellular matrix (ECM) mechanics and changes in cell shape, are transmitted to the nucleus directly or indirectly to orchestrate transcriptional activities that are crucial for embryogenesis and organogenesis. In this Commentary, we review how the mechanical control of gene transcription contributes to the maintenance of pluripotency, determination of cell fate, pattern formation and organogenesis, as well as how it is involved in the control of cell and tissue function throughout embryogenesis and adult life. A deeper understanding of these mechanosensitive transcriptional control mechanisms should lead to new approaches to tissue engineering and regenerative medicine.

  17. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    Adipocyte differentiation is regulated by a complex cascade of signals that drive the transcriptional reprogramming of the fibroblastic precursors. Genome-wide analyses of chromatin accessibility and binding of adipogenic transcription factors make it possible to generate "snapshots" of the trans...

  18. Structural basis of transcription activation.

    Science.gov (United States)

    Feng, Yu; Zhang, Yu; Ebright, Richard H

    2016-06-10

    Class II transcription activators function by binding to a DNA site overlapping a core promoter and stimulating isomerization of an initial RNA polymerase (RNAP)-promoter closed complex into a catalytically competent RNAP-promoter open complex. Here, we report a 4.4 angstrom crystal structure of an intact bacterial class II transcription activation complex. The structure comprises Thermus thermophilus transcription activator protein TTHB099 (TAP) [homolog of Escherichia coli catabolite activator protein (CAP)], T. thermophilus RNAP σ(A) holoenzyme, a class II TAP-dependent promoter, and a ribotetranucleotide primer. The structure reveals the interactions between RNAP holoenzyme and DNA responsible for transcription initiation and reveals the interactions between TAP and RNAP holoenzyme responsible for transcription activation. The structure indicates that TAP stimulates isomerization through simple, adhesive, stabilizing protein-protein interactions with RNAP holoenzyme. Copyright © 2016, American Association for the Advancement of Science.

  19. Structural basis of transcription elongation.

    Science.gov (United States)

    Martinez-Rucobo, Fuensanta W; Cramer, Patrick

    2013-01-01

    For transcription elongation, all cellular RNA polymerases form a stable elongation complex (EC) with the DNA template and the RNA transcript. Since the millennium, a wealth of structural information and complementary functional studies provided a detailed three-dimensional picture of the EC and many of its functional states. Here we summarize these studies that elucidated EC structure and maintenance, nucleotide selection and addition, translocation, elongation inhibition, pausing and proofreading, backtracking, arrest and reactivation, processivity, DNA lesion-induced stalling, lesion bypass, and transcriptional mutagenesis. In the future, additional structural and functional studies of elongation factors that control the EC and their possible allosteric modes of action should result in a more complete understanding of the dynamic molecular mechanisms underlying transcription elongation. This article is part of a Special Issue entitled: RNA polymerase II Transcript Elongation. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Thermodynamic Model of Transcription Elongation

    Science.gov (United States)

    Tadigotla, Vasisht; O'Maoileidigh, Daibhid; Sengupta, Anirvan; Epshtein, Vitaly; Ebright, Richard; Nudler, Evgeny; Ruckenstein, Andrei

    2006-03-01

    We present a statistical mechanics approach to the prediction of backtracked pauses in prokaryotic transcription elongation derived from structural models of the transcription elongation complex (TEC). Our algorithm is based on the thermodynamic stability of TEC along the DNA template calculated from the sequence dependent free-energy of DNA-DNA, DNA-RNA and RNA-RNA base pairing associated with (a) the translocation and size fluctuations of the transcription bubble; (b) the changes in the DNA-RNA hybrid; and (c) the changes in the RNA folding free-energy. The calculations involve no adjustable parameters apart from a cutoff used to discriminate paused from non-paused complexes. When applied to 100 experimental pauses in transcription elongation by E. coli RNA polymerase on ten DNA templates the approach produces highly statistically significant results. Transcription elongation is an inherently kinetic process and a simplified kinetic model with the same predictive power is presented separately.

  1. ETS transcription factors in hematopoietic stem cell development.

    Science.gov (United States)

    Ciau-Uitz, Aldo; Wang, Lu; Patient, Roger; Liu, Feng

    2013-12-01

    Hematopoietic stem cells (HSCs) are essential for the maintenance of the hematopoietic system. However, these cells cannot be maintained or created in vitro, and very little is known about their generation during embryogenesis. Many transcription factors and signaling pathways play essential roles at various stages of HSC development. Members of the ETS ('E twenty-six') family of transcription factors are recognized as key regulators within the gene regulatory networks governing hematopoiesis, including the ontogeny of HSCs. Remarkably, although all ETS transcription factors bind the same DNA consensus sequence and overlapping tissue expression is observed, individual ETS transcription factors play unique roles in the development of HSCs. Also, these transcription factors are recurrently used throughout development and their functions are context-dependent, increasing the challenge of studying their mechanism of action. Critically, ETS factors also play roles under pathological conditions, such as leukemia and, therefore, deciphering their mechanism of action will not only enhance our knowledge of normal hematopoiesis, but also inform protocols for their creation in vitro from pluripotent stem cells and the design of new therapeutic approaches for the treatment of malignant blood cell diseases. In this review, we summarize the key findings on the roles of ETS transcription factors in HSC development and discuss novel mechanisms by which they could control hematopoiesis. © 2013.

  2. Emerging Functions of Transcription Factors in Malaria Parasite

    Directory of Open Access Journals (Sweden)

    Renu Tuteja

    2011-01-01

    Full Text Available Transcription is a process by which the genetic information stored in DNA is converted into mRNA by enzymes known as RNA polymerase. Bacteria use only one RNA polymerase to transcribe all of its genes while eukaryotes contain three RNA polymerases to transcribe the variety of eukaryotic genes. RNA polymerase also requires other factors/proteins to produce the transcript. These factors generally termed as transcription factors (TFs are either associated directly with RNA polymerase or add in building the actual transcription apparatus. TFs are the most common tools that our cells use to control gene expression. Plasmodium falciparum is responsible for causing the most lethal form of malaria in humans. It shows most of its characteristics common to eukaryotic transcription but it is assumed that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes. In this article we describe the studies on the main TFs such as myb protein, high mobility group protein and ApiA2 family proteins from malaria parasite. These studies show that these TFs are slowly emerging to have defined roles in the regulation of gene expression in the parasite.

  3. Potential Role of Activating Transcription Factor 5 during Osteogenesis

    Directory of Open Access Journals (Sweden)

    Luisa Vicari

    2016-01-01

    Full Text Available Human adipose-derived stem cells are an abundant population of stem cells readily isolated from human adipose tissue that can differentiate into connective tissue lineages including bone, cartilage, fat, and muscle. Activating transcription factor 5 is a transcription factor of the ATF/cAMP response element-binding protein (CREB family. It is transcribed in two types of mRNAs (activating transcription factor 5 isoform 1 and activating transcription factor 5 isoform 2, encoding the same single 30-kDa protein. Although it is well demonstrated that it regulates the proliferation, differentiation, and apoptosis, little is known about its potential role in osteogenic differentiation. The aim of this study was to evaluate the expression levels of the two isoforms and protein during osteogenic differentiation of human adipose-derived stem cells. Our data indicate that activating transcription factor 5 is differentially expressed reaching a peak of expression at the stage of bone mineralization. These findings suggest that activating transcription factor 5 could play an interesting regulatory role during osteogenesis, which would provide a powerful tool to study bone physiology.

  4. Tead and AP1 Coordinate Transcription and Motility.

    Science.gov (United States)

    Liu, Xiangfan; Li, Huapeng; Rajurkar, Mihir; Li, Qi; Cotton, Jennifer L; Ou, Jianhong; Zhu, Lihua J; Goel, Hira L; Mercurio, Arthur M; Park, Joo-Seop; Davis, Roger J; Mao, Junhao

    2016-02-09

    The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1-3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Tead and AP1 Coordinate Transcription and Motility

    Directory of Open Access Journals (Sweden)

    Xiangfan Liu

    2016-02-01

    Full Text Available The Tead family transcription factors are the major intracellular mediators of the Hippo-Yap pathway. Despite the importance of Hippo signaling in tumorigenesis, Tead-dependent downstream oncogenic programs and target genes in cancer cells remain poorly understood. Here, we characterize Tead4-mediated transcriptional networks in a diverse range of cancer cells, including neuroblastoma, colorectal, lung, and endometrial carcinomas. By intersecting genome-wide chromatin occupancy analyses of Tead4, JunD, and Fra1/2, we find that Tead4 cooperates with AP1 transcription factors to coordinate target gene transcription. We find that Tead-AP1 interaction is JNK independent but engages the SRC1–3 co-activators to promote downstream transcription. Furthermore, we show that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion. Together, our data unveil a critical regulatory mechanism underlying Tead- and AP1-controlled transcriptional and functional outputs in cancer cells.

  6. Learning about Familial Hypercholesterolemia

    Science.gov (United States)

    ... terms used on this page Learning About Familial Hypercholesterolemia What is familial hypercholesterolemia? What are the symptoms ... Additional Resources About Familial Hypercholesterolemia What is familial hypercholesterolemia? Familial hypercholesterolemia is an inherited condition that causes ...

  7. Natural Family Planning

    Science.gov (United States)

    ... Sex and Birth Control Birth Control Natural Family Planning Natural Family Planning Birth ControlPrevention and WellnessSex and Birth Control Share Natural Family Planning Natural Family PlanningWhat is natural family planning?Natural ...

  8. A new role for LOX and LOXL2 proteins in transcription regulation.

    Science.gov (United States)

    Iturbide, Ane; García de Herreros, Antonio; Peiró, Sandra

    2015-05-01

    The lysyl oxidase (LOX) family of proteins (LOX and LOXL1-LOXL4) oxidize amino groups located in the ε-position in lysines to generate an aldehyde group. In general, they are considered as extracellular proteins and have elastin and collagen as their main substrates. However, recent findings suggest a critical intracellular role for LOX and LOXL2 in transcriptional regulation. In this review, we highlight what is known about the transcriptional role of these two members of the family. Intriguingly, both the intracellular localization of these proteins and the fact that histones have been revealed to be their substrates place this family of proteins within the epigenetic field.

  9. [Family violence].

    Science.gov (United States)

    Manoudi, F; Chagh, R; Es-soussi, M; Asri, F; Tazi, I

    2013-09-01

    Family violence is a serious public health problem, the scale of which is seriously increasing in Morocco. Although it has existed for a long time, we ignore the real characteristics of this plague in our country; our work consisted in an epidemiological approach of family violence in Marrakech during 2006. After elaborating a questionnaire, which allows the study of the demographic and social profile of the families, the study of violence exercised in the family and the evaluation of the depression in the women, we led an inquiry amongst 265 women. Analysis of the results obtained has allowed us to underline the following characteristics: 16.6% of the women in our sample had been physically beaten; the young age is a risk factor; the age range most affected by violence is in women between the ages of 30 and 40 and which represent 39% of the battered women; domestic violence touches all the social, economic and cultural classes: in our study, 63% of the women having undergone violence were housewives, 25% were managers and 3% senior executives; family problems were the most important cause of violence in our study, representing 32.32%. Requests for money was the cause in 11.3% of the cases, and imposed sexual relations were found in 6.8% of the cases; alcoholism is an aggravating factor of family violence; 27.3% of the spouses who assaulted their wives were drunk; 52% of the assaulted women were victims of violence in childhood and 36% had been witness to their father's violence; in 63.6% of the cases of violence, the children were witnesses, and in 25% of the cases the children were victims of violence at the same time as their mothers; 50% of the women victims of violence did not react, while 38.6% left home, and 9.1 filed for divorce. Thirty-two percent of the assaulted woman had been traumatised by the aggression; the association of depression and violence was very high, 343% of the battered women in our study suffered from severe depression. This work

  10. My family

    Institute of Scientific and Technical Information of China (English)

    陈君怡

    2011-01-01

    I have a happy fam_ly.Lookthis is my family photo.This is mydad.He often wears a pair Ofglasses(戴着一副眼镜I_This ismy mum.She is very pretty.Sheloves me very much.The little girlin a red blouse is me.I’m smiling(微笑).I love my family.

  11. [Familial hypercholesterolemia].

    Science.gov (United States)

    Turpin, G; Bruckert, E

    1999-12-01

    Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.

  12. NAC Transcription Factors in Stress Responses and Senescence

    DEFF Research Database (Denmark)

    O'Shea, Charlotte

    in Arabidopsis as a prerequisite for a system-wide understanding of NAC transcription factors. This PhD thesis contributes to the work through the production and purification of NAC domain recombinant proteins. More importantly, the work presented here has created a platform for future verification of predicted......Plant-specific NAM/ATAF/CUC (NAC) transcription factors have recently received considerable attention due to their significant roles in plant development and stress signalling. This interest has resulted in a number of physiological, genetic and cell biological studies of their functions. Some...... not involve significant folding-upon-binding but fuzziness or an extended ANAC046 region. The ANAC046 regulatory domain functions as an entropic chain with a bait for interactions with for example RCD1. RCD1 interacts with transcription factors from several different families, and the large stress...

  13. Transcriptional mechanisms coordinating tight junction assembly during epithelial differentiation.

    Science.gov (United States)

    Boivin, Felix J; Schmidt-Ott, Kai M

    2017-06-01

    Epithelial tissues form a selective barrier via direct cell-cell interactions to separate and establish concentration gradients between the different compartments of the body. Proper function and formation of this barrier rely on the establishment of distinct intercellular junction complexes. These complexes include tight junctions, adherens junctions, desmosomes, and gap junctions. The tight junction is by far the most diverse junctional complex in the epithelial barrier. Its composition varies greatly across different epithelial tissues to confer various barrier properties. Thus, epithelial cells rely on tightly regulated transcriptional mechanisms to ensure proper formation of the epithelial barrier and to achieve tight junction diversity. Here, we review different transcriptional mechanisms utilized during embryogenesis and disease development to promote tight junction assembly and maintenance of intercellular barrier integrity. We focus particularly on the Grainyhead-like transcription factors and ligand-activated nuclear hormone receptors, two central families of proteins in epithelialization. © 2017 New York Academy of Sciences.

  14. Transcription regulation mechanisms of bacteriophages

    Science.gov (United States)

    Yang, Haiquan; Ma, Yingfang; Wang, Yitian; Yang, Haixia; Shen, Wei; Chen, Xianzhong

    2014-01-01

    Phage diversity significantly contributes to ecology and evolution of new bacterial species through horizontal gene transfer. Therefore, it is essential to understand the mechanisms underlying phage-host interactions. After initial infection, the phage utilizes the transcriptional machinery of the host to direct the expression of its own genes. This review presents a view on the transcriptional regulation mechanisms of bacteriophages, and its contribution to phage diversity and classification. Through this review, we aim to broaden the understanding of phage-host interactions while providing a reference source for researchers studying the regulation of phage transcription. PMID:25482231

  15. Sigma Factors for Cyanobacterial Transcription

    Directory of Open Access Journals (Sweden)

    Sousuke Imamura

    2009-04-01

    Full Text Available Cyanobacteria are photosynthesizing microorganisms that can be used as a model for analyzing gene expression. The expression of genes involves transcription and translation. Transcription is performed by the RNA polymerase (RNAP holoenzyme, comprising a core enzyme and a sigma (σ factor which confers promoter selectivity. The unique structure, expression, and function of cyanobacterial σ factors (and RNAP core subunits are summarized here based on studies, reported previously. The types of promoter recognized by the σ factors are also discussed with regard to transcriptional regulation.

  16. Structural insights into the transcription-independent apoptotic pathway of p53.

    Science.gov (United States)

    Chi, Seung-Wook

    2014-03-01

    Reactivating the p53 pathway in tumors is an important strategy for anticancer therapy. In response to diverse cellular stresses, the tumor suppressor p53 mediates apoptosis in a transcription-independent and transcription-dependent manner. Although extensive studies have focused on the transcription-dependent apoptotic pathway of p53, the transcription-independent apoptotic pathway of p53 has only recently been discovered. Molecular interactions between p53 and Bcl-2 family proteins in the mitochondria play an essential role in the transcription-independent apoptosis of p53. This review describes the structural basis for the transcription-independent apoptotic pathway of p53 and discusses its potential application to anticancer therapy.

  17. Gfi1 and gfi1b repress rag transcription in plasmacytoid dendritic cells in vitro.

    Directory of Open Access Journals (Sweden)

    Kwan T Chow

    Full Text Available Growth factor independence genes (Gfi1 and Gfi1b repress recombination activating genes (Rag transcription in developing B lymphocytes. Because all blood lineages originate from hematopoietic stem cells (HSCs and different lineage progenitors have been shown to share transcription factor networks prior to cell fate commitment, we hypothesized that GFI family proteins may also play a role in repressing Rag transcription or a global lymphoid transcriptional program in other blood lineages. We tested the level of Rag transcription in various blood cells when Gfi1 and Gfi1b were deleted, and observed an upregulation of Rag expression in plasmacytoid dendritic cells (pDCs. Using microarray analysis, we observed that Gfi1 and Gfi1b do not regulate a lymphoid or pDC-specific transcriptional program. This study establishes a role for Gfi1 and Gfi1b in Rag regulation in a non-B lineage cell type.

  18. Fission yeast CSL proteins function as transcription factors.

    Directory of Open Access Journals (Sweden)

    Martina Oravcová

    Full Text Available BACKGROUND: Transcription factors of the CSL (CBF1/RBP-Jk/Suppressor of Hairless/LAG-1 family are key regulators of metazoan development and function as the effector components of the Notch receptor signalling pathway implicated in various cell fate decisions. CSL proteins recognize specifically the GTG[G/A]AA sequence motif and several mutants compromised in their ability to bind DNA have been reported. In our previous studies we have identified a number of novel putative CSL family members in fungi, organisms lacking the Notch pathway. It is not clear whether these represent genuine CSL family members. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of in vitro and in vivo approaches we characterized the DNA binding properties of Cbf11 and Cbf12, the antagonistic CSL paralogs from the fission yeast, important for the proper coordination of cell cycle events and the regulation of cell adhesion. We have shown that a mutation of a conserved arginine residue abolishes DNA binding in both CSL paralogs, similar to the situation in mouse. We have also demonstrated the ability of Cbf11 and Cbf12 to activate gene expression in an autologous fission yeast reporter system. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the fission yeast CSL proteins are indeed genuine family members capable of functioning as transcription factors, and provide support for the ancient evolutionary origin of this important protein family.

  19. Region 4 of sigma as a target for transcription regulation.

    Science.gov (United States)

    Dove, Simon L; Darst, Seth A; Hochschild, Ann

    2003-05-01

    Bacterial sigma factors play a key role in promoter recognition, making direct contact with conserved promoter elements. Most sigma factors belong to the sigma70 family, named for the primary sigma factor in Escherichia coli. Members of the sigma70 family typically share four conserved regions and, here, we focus on region 4, which is directly involved in promoter recognition and serves as a target for a variety of regulators of transcription initiation. We review recent advances in the understanding of the mechanism of action of regulators that target region 4 of sigma.

  20. HIF transcription factors, inflammation, and immunity.

    Science.gov (United States)

    Palazon, Asis; Goldrath, Ananda W; Nizet, Victor; Johnson, Randall S

    2014-10-16

    The hypoxic response in cells and tissues is mediated by the family of hypoxia-inducible factor (HIF) transcription factors; these play an integral role in the metabolic changes that drive cellular adaptation to low oxygen availability. HIF expression and stabilization in immune cells can be triggered by hypoxia, but also by other factors associated with pathological stress: e.g., inflammation, infectious microorganisms, and cancer. HIF induces a number of aspects of host immune function, from boosting phagocyte microbicidal capacity to driving T cell differentiation and cytotoxic activity. Cellular metabolism is emerging as a key regulator of immunity, and it constitutes another layer of fine-tuned immune control by HIF that can dictate myeloid cell and lymphocyte development, fate, and function. Here we discuss how oxygen sensing in the immune microenvironment shapes immunological response and examine how HIF and the hypoxia pathway control innate and adaptive immunity.

  1. The cullin protein family.

    Science.gov (United States)

    Sarikas, Antonio; Hartmann, Thomas; Pan, Zhen-Qiang

    2011-01-01

    Cullin proteins are molecular scaffolds that have crucial roles in the post-translational modification of cellular proteins involving ubiquitin. The mammalian cullin protein family comprises eight members (CUL1 to CUL7 and PARC), which are characterized by a cullin homology domain. CUL1 to CUL7 assemble multi-subunit Cullin-RING E3 ubiquitin ligase (CRL) complexes, the largest family of E3 ligases with more than 200 members. Although CUL7 and PARC are present only in chordates, other members of the cullin protein family are found in Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana and yeast. A cullin protein tethers both a substrate-targeting unit, often through an adaptor protein, and the RING finger component in a CRL. The cullin-organized CRL thus positions a substrate close to the RING-bound E2 ubiquitin-conjugating enzyme, which catalyzes the transfer of ubiquitin to the substrate. In addition, conjugation of cullins with the ubiquitin-like molecule Nedd8 modulates activation of the corresponding CRL complex, probably through conformational regulation of the interactions between cullin's carboxy-terminal tail and CRL's RING subunit. Genetic studies in several model organisms have helped to unravel a multitude of physiological functions associated with cullin proteins and their respective CRLs. CRLs target numerous substrates and thus have an impact on a range of biological processes, including cell growth, development, signal transduction, transcriptional control, genomic integrity and tumor suppression. Moreover, mutations in CUL7 and CUL4B genes have been linked to hereditary human diseases.

  2. Transcriptional, post-transcriptional and post-translational regulations of gene expression during leaf polarity formation

    Institute of Scientific and Technical Information of China (English)

    Lin Xu; Li Yang; Hai Huang

    2007-01-01

    Leaf morphogenesis requires the establishment of adaxial-abaxial polarity after primordium initiation from the shoot apical meristem (SAM). Several families of transcription factors are known to play critical roles in promoting adaxial or abaxial leaf fate. Recently, post-transcriptional gene silencing pathways have been shown to regulate the establishment of leaf polarity, providing novel and exciting insights into leaf development. For example, microRNAs (miR165/166)and a trans-acting siRNA (TAS3-derived tasiR-ARF) have been shown to repress the expression of several key transcription factor genes. In addition, yet another level of regulation, post-translational regulation, has been revealed recently by studies on the role of the 26S proteasome in leaf polarity. Although our understanding regarding the molecular mechanisms underlying establishment of adaxial-abaxial polarity has greatly improved, there is still much that remains elusive.This review aims to discuss recent progress, as well as the remaining questions, regarding the molecular mechanisms underlying leaf polarity formation.

  3. Women's hidden transcripts about abortion in Brazil.

    Science.gov (United States)

    Nations, M K; Misago, C; Fonseca, W; Correia, L L; Campbell, O M

    1997-06-01

    Two folk medical conditions, "delayed" (atrasada) and "suspended" (suspendida) menstruation, are described as perceived by poor Brazilian women in Northeast Brazil. Culturally prescribed methods to "regulate" these conditions and provoke menstrual bleeding are also described, including ingesting herbal remedies, patent drugs, and modern pharmaceuticals. The ingestion of such self-administered remedies is facilitated by the cognitive ambiguity, euphemisms, folklore, etc., which surround conception and gestation. The authors argue that the ethnomedical conditions of "delayed" and "suspended" menstruation and subsequent menstrual regulation are part of the "hidden reproductive transcript" of poor and powerless Brazilian women. Through popular culture, they voice their collective dissent to the official, public opinion about the illegality and immorality of induced abortion and the chronic lack of family planning services in Northeast Brazil. While many health professionals consider women's explanations of menstrual regulation as a "cover-up" for self-induced abortions, such popular justifications may represent either an unconscious or artful manipulation of hegemonic, anti-abortion ideology expressed in prudent, unobtrusive and veiled ways. The development of safer abortion alternatives should consider women's hidden reproductive transcripts.

  4. Mitochondrial nucleoid and transcription factor A.

    Science.gov (United States)

    Kanki, Tomotake; Nakayama, Hiroshi; Sasaki, Narie; Takio, Koji; Alam, Tanfis Istiaq; Hamasaki, Naotaka; Kang, Dongchon

    2004-04-01

    Nuclear DNA is tightly packed into nucleosomal structure. In contrast, human mitochondrial DNA (mtDNA) had long been believed to be rather naked because mitochondria lack histone. Mitochondrial transcription factor A (TFAM), a member of a high mobility group (HMG) protein family and a first-identified mitochondrial transcription factor, is essential for maintenance of mitochondrial DNA. Abf2, a yeast counterpart of human TFAM, is abundant enough to cover the whole region of mtDNA and to play a histone-like role in mitochondria. Human TFAM is indeed as abundant as Abf2, suggesting that TFAM also has a histone-like architectural role for maintenance of mtDNA. When human mitochondria are solubilized with non-ionic detergent Nonidet-P40 and then separated into soluble and particulate fractions, most TFAM is recovered from the particulate fraction together with mtDNA, suggesting that human mtDNA forms a nucleoid structure. TFAM is tightly associated with mtDNA as a main component of the nucleoid.

  5. Teratogenic factors affect transcription factor expression.

    Science.gov (United States)

    Kojima, Takuya; Asano, Shinya; Takahashi, Naoki

    2013-01-01

    Chemical compounds are produced every day, many with adverse effects on human health, and hence it is vital to predict the risks to humans simply, rapidly, and accurately. Teratogens have a serious impact on fetal development. This has been studied mainly by phenotypic analysis of experimental animals. However, since phenotypes can vary within different species, we established a new evaluation system based on our recent finding that teratogens influence Hox gene expression in mice. Similarly to the Hox gene expression changes, the expression patterns of several transcription factors involved in development, including the Dlx, Irx, Sall, and T-box families, were altered after 6 h of exposure to retinoic acid (RA) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The expression changes in Dlx4, Dlx6, Irx5, Sall2, Sall3, Sall4, Tbx10, and Tbx22 were linked to teratogen-induced phenotypes, and our results indicate that expression changes in developmental transcription factors can help to predict teratogenic risk.

  6. Transcription profiling reveals stage- and function-dependent expression patterns in the filarial nematode Brugia malayi

    Directory of Open Access Journals (Sweden)

    Li Ben-Wen

    2012-05-01

    Full Text Available Abstract Background Brugia malayi is a nematode parasite that causes lymphatic filariasis, a disfiguring and disabiling tropical disease. Although a first draft genome sequence was released in 2007, very little is understood about transcription programs that govern developmental changes required for the parasite’s development and survival in its mammalian and insect hosts. Results We used a microarray with probes that represent some 85% of predicted genes to generate gene expression profiles for seven parasite life cycle stages/sexes. Approximately 41% of transcripts with detectable expression signals were differentially expressed across lifecycle stages. Twenty-six percent of transcripts were exclusively expressed in a single parasite stage, and 27% were expressed in all stages studied. K-means clustering of differentially expressed transcripts revealed five major transcription patterns that were associated with parasite lifecycle stages or gender. Examination of known stage-associated transcripts validated these data sets and suggested that newly identified stage or gender-associated transcripts may exercise biological functions in development and reproduction. The results also indicate that genes with similar transcription patterns were often involved in similar functions or cellular processes. For example, nuclear receptor family gene transcripts were upregulated in gene expression pattern four (female-enriched while protein kinase gene family transcripts were upregulated in expression pattern five (male-enriched. We also used pair-wise comparisons to identify transcriptional changes between life cycle stages and sexes. Conclusions Analysis of gene expression patterns of lifecycle in B. malayi has provided novel insights into the biology of filarial parasites. Proteins encoded by stage-associated and/or stage-specific transcripts are likely to be critically important for key parasite functions such as establishment and maintenance of

  7. RNA-guided transcriptional regulation

    Energy Technology Data Exchange (ETDEWEB)

    Church, George M.; Mali, Prashant G.; Esvelt, Kevin M.

    2016-02-23

    Methods of modulating expression of a target nucleic acid in a cell are provided including introducing into the cell a first foreign nucleic acid encoding one or more RNAs complementary to DNA, wherein the DNA includes the target nucleic acid, introducing into the cell a second foreign nucleic acid encoding a nuclease-null Cas9 protein that binds to the DNA and is guided by the one or more RNAs, introducing into the cell a third foreign nucleic acid encoding a transcriptional regulator protein or domain, wherein the one or more RNAs, the nuclease-null Cas9 protein, and the transcriptional regulator protein or domain are expressed, wherein the one or more RNAs, the nuclease-null Cas9 protein and the transcriptional regulator protein or domain co-localize to the DNA and wherein the transcriptional regulator protein or domain regulates expression of the target nucleic acid.

  8. The eukaryotic gene transcription machinery.

    Science.gov (United States)

    Kornberg, R D

    2001-08-01

    Seven purified proteins may be combined to reconstitute regulated, promoter-dependent RNA polymerase II transcription: five general transcription factors, Mediator, and RNA polymerase II. The entire system has been conserved across species from yeast to humans. The structure of RNA polymerase II, consisting of 10 polypeptides with a mass of about 500 kDa, has been determined at atomic resolution. On the basis of this structure, that of an actively transcribing RNA polymerase II complex has been determined as well.

  9. Establishment of an in vitro transcription system for Peste des petits ruminant virus

    Directory of Open Access Journals (Sweden)

    Yunus Mohammad

    2012-12-01

    Full Text Available Abstract Background Peste-des-petits ruminants virus (PPRV is a non segmented negative strand RNA virus of the genus Morbillivirus within Paramyxoviridae family. Negative strand RNA viruses are known to carry nucleocapsid (N protein, phospho (P protein and RNA polymerase (L protein packaged within the virion which possess all activities required for transcription, post-transcriptional modification of mRNA and replication. In order to understand the mechanism of transcription and replication of the virus, an in vitro transcription reconstitution system is required. In the present work, an in vitro transcription system has been developed with ribonucleoprotein (RNP complex purified from virus infected cells as well as partially purified recombinant polymerase (L-P complex from insect cells along with N-RNA (genomic RNA encapsidated by N protein template isolated from virus infected cells. Results RNP complex isolated from virus infected cells and recombinant L-P complex purified from insect cells was used to reconstitute transcription on N-RNA template. The requirement for this transcription reconstitution has been defined. Transcription of viral genes in the in vitro system was confirmed by PCR amplification of cDNAs corresponding to individual transcripts using gene specific primers. In order to measure the relative expression level of viral transcripts, real time PCR analysis was carried out. qPCR analysis of the transcription products made in vitro showed a gradient of polarity of transcription from 3’ end to 5’ end of the genome similar to that exhibited by the virus in infected cells. Conclusion This report describes for the first time, the development of an in vitro transcription reconstitution system for PPRV with RNP complex purified from infected cells and recombinant L-P complex expressed in insect cells. Both the complexes were able to synthesize all the mRNA species in vitro, exhibiting a gradient of polarity in transcription.

  10. Thermodynamic and Kinetic Modeling of Transcriptional Pausing

    National Research Council Canada - National Science Library

    Vasisht R. Tadigotla; Dáibhid Ó. Maoiléidigh; Anirvan M. Sengupta; Vitaly Epshtein; Richard H. Ebright; Evgeny Nudler; Andrei E. Ruckenstein

    2006-01-01

    We present a statistical mechanics approach for the prediction of backtracked pauses in bacterial transcription elongation derived from structural models of the transcription elongation complex (EC...

  11. National Capital Planning Commission Meeting Transcripts

    Data.gov (United States)

    National Capital Planning Commission — Transcripts of the monthly (with the exception of August) National Capital Planning Commission meeting transcripts are provided for research to confirm actions taken...

  12. Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq.

    Directory of Open Access Journals (Sweden)

    Augix Guohua Xu

    Full Text Available Transcription is the first step connecting genetic information with an organism's phenotype. While expression of annotated genes in the human brain has been characterized extensively, our knowledge about the scope and the conservation of transcripts located outside of the known genes' boundaries is limited. Here, we use high-throughput transcriptome sequencing (RNA-Seq to characterize the total non-ribosomal transcriptome of human, chimpanzee, and rhesus macaque brain. In all species, only 20-28% of non-ribosomal transcripts correspond to annotated exons and 20-23% to introns. By contrast, transcripts originating within intronic and intergenic repetitive sequences constitute 40-48% of the total brain transcriptome. Notably, some repeat families show elevated transcription. In non-repetitive intergenic regions, we identify and characterize 1,093 distinct regions highly expressed in the human brain. These regions are conserved at the RNA expression level across primates studied and at the DNA sequence level across mammals. A large proportion of these transcripts (20% represents 3'UTR extensions of known genes and may play roles in alternative microRNA-directed regulation. Finally, we show that while transcriptome divergence between species increases with evolutionary time, intergenic transcripts show more expression differences among species and exons show less. Our results show that many yet uncharacterized evolutionary conserved transcripts exist in the human brain. Some of these transcripts may play roles in transcriptional regulation and contribute to evolution of human-specific phenotypic traits.

  13. Understanding Transcription Factor Regulation by Integrating Gene Expression and DNase I Hypersensitive Sites

    Directory of Open Access Journals (Sweden)

    Guohua Wang

    2015-01-01

    Full Text Available Transcription factors are proteins that bind to DNA sequences to regulate gene transcription. The transcription factor binding sites are short DNA sequences (5–20 bp long specifically bound by one or more transcription factors. The identification of transcription factor binding sites and prediction of their function continue to be challenging problems in computational biology. In this study, by integrating the DNase I hypersensitive sites with known position weight matrices in the TRANSFAC database, the transcription factor binding sites in gene regulatory region are identified. Based on the global gene expression patterns in cervical cancer HeLaS3 cell and HelaS3-ifnα4h cell (interferon treatment on HeLaS3 cell for 4 hours, we present a model-based computational approach to predict a set of transcription factors that potentially cause such differential gene expression. Significantly, 6 out 10 predicted functional factors, including IRF, IRF-2, IRF-9, IRF-1 and IRF-3, ICSBP, belong to interferon regulatory factor family and upregulate the gene expression levels responding to the interferon treatment. Another factor, ISGF-3, is also a transcriptional activator induced by interferon alpha. Using the different transcription factor binding sites selected criteria, the prediction result of our model is consistent. Our model demonstrated the potential to computationally identify the functional transcription factors in gene regulation.

  14. The Olig family affects central nervous system development and disease

    Institute of Scientific and Technical Information of China (English)

    Botao Tan; Jing Yu; Ying Yin; Gongwei Jia; Wei Jiang; Lehua Yu

    2014-01-01

    Neural cell differentiation and maturation is a critical step during central nervous system devel-opment. The oligodendrocyte transcription family (Olig family) is known to be an important factor in regulating neural cell differentiation. Because of this, the Olig family also affects acute and chronic central nervous system diseases, including brain injury, multiple sclerosis, and even gliomas. Improved understanding about the functions of the Olig family in central nervous system development and disease will greatly aid novel breakthroughs in central nervous system diseases. This review investigates the role of the Olig family in central nervous system develop-ment and related diseases.

  15. Identification and Transcript Analysis of the TCP Transcription Factors in the Diploid Woodland Strawberry Fragaria vesca

    Science.gov (United States)

    Wei, Wei; Hu, Yang; Cui, Meng-Yuan; Han, Yong-Tao; Gao, Kuan; Feng, Jia-Yue

    2016-01-01

    Plant-specific TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (TCP) transcription factors play versatile functions in multiple processes of plant growth and development. However, no systematic study has been performed in strawberry. In this study, 19 FvTCP genes were identified in the diploid woodland strawberry (Fragaria vesca) accession Heilongjiang-3. Phylogenetic analysis suggested that the FvTCP genes were classified into two main classes, with the second class further divided into two subclasses, which was supported by the exon-intron organizations and the conserved motif structures. Promoter analysis revealed various cis-acting elements related to growth and development, hormone and/or stress responses. We analyzed FvTCP gene transcript accumulation patterns in different tissues and fruit developmental stages. Among them, 12 FvTCP genes exhibited distinct tissue-specific transcript accumulation patterns. Eleven FvTCP genes were down-regulated in different fruit developmental stages, while five FvTCP genes were up-regulated. Transcripts of FvTCP genes also varied with different subcultural propagation periods and were induced by hormone treatments and biotic and abiotic stresses. Subcellular localization analysis showed that six FvTCP-GFP fusion proteins showed distinct localizations in Arabidopsis mesophyll protoplasts. Notably, transient over-expression of FvTCP9 in strawberry fruits dramatically affected the expression of a series of genes implicated in fruit development and ripening. Taken together, the present study may provide the basis for functional studies to reveal the role of this gene family in strawberry growth and development. PMID:28066489

  16. TEAD transcription factors are required for normal primary myoblast differentiation in vitro and muscle regeneration in vivo

    OpenAIRE

    Shilpy Joshi; Guillaume Davidson; Stéphanie Le Gras; Shuichi Watanabe; Thomas Braun; Gabrielle Mengus; Irwin Davidson

    2017-01-01

    The TEAD family of transcription factors (TEAD1-4) bind the MCAT element in the regulatory elements of both growth promoting and myogenic differentiation genes. Defining TEAD transcription factor function in myogenesis has proved elusive due to overlapping expression of family members and their functional redundancy. We show that silencing of either Tead1, Tead2 or Tead4 did not effect primary myoblast (PM) differentiation, but that their simultaneous knockdown strongly impaired differentiati...

  17. Navigating the transcriptional roadmap regulating plant secondary cell wall deposition

    Directory of Open Access Journals (Sweden)

    Steven Grant Hussey

    2013-08-01

    Full Text Available The current status of lignocellulosic biomass as an invaluable resource in industry, agriculture and health has spurred increased interest in understanding the transcriptional regulation of secondary cell wall (SCW biosynthesis. The last decade of research has revealed an extensive network of NAC, MYB and other families of transcription factors regulating Arabidopsis SCW biosynthesis, and numerous studies have explored SCW-related transcription factors in other dicots and monocots. Whilst the general structure of the Arabidopsis network has been a topic of several reviews, they have not comprehensively represented the detailed protein-DNA and protein-protein interactions described in the literature, and an understanding of network dynamics and functionality has not yet been achieved for SCW formation. Furthermore the methodologies employed in studies of SCW transcriptional regulation have not received much attention, especially in the case of non-model organisms. In this review, we have reconstructed the most exhaustive literature-based network representations to date of SCW transcriptional regulation in Arabidopsis. We include a manipulable Cytoscape representation of the Arabidopsis SCW transcriptional network to aid in future studies, along with a list of supporting literature for each documented interaction. Amongst other topics, we discuss the various components of the network, its evolutionary conservation in plants, putative modules and dynamic mechanisms that may influence network function, and the approaches that have been employed in network inference. Future research should aim to better understand network function and its response to dynamic perturbations, whilst the development and application of genome-wide approaches such as ChIP-seq and systems genetics are in progress for the study of SCW transcriptional regulation in non-model organisms.

  18. Transcriptional programs controlling perinatal lung maturation.

    Directory of Open Access Journals (Sweden)

    Yan Xu

    Full Text Available The timing of lung maturation is controlled precisely by complex genetic and cellular programs. Lung immaturity following preterm birth frequently results in Respiratory Distress Syndrome (RDS and Broncho-Pulmonary Dysplasia (BPD, which are leading causes of mortality and morbidity in preterm infants. Mechanisms synchronizing gestational length and lung maturation remain to be elucidated. In this study, we designed a genome-wide mRNA expression time-course study from E15.5 to Postnatal Day 0 (PN0 using lung RNAs from C57BL/6J (B6 and A/J mice that differ in gestational length by ∼30 hr (B6transcriptional networks controlling lung maturation. We identified both temporal and strain dependent gene expression patterns during lung maturation. For time dependent changes, cell adhesion, vasculature development, and lipid metabolism/transport were major bioprocesses induced during the saccular stage of lung development at E16.5-E17.5. CEBPA, PPARG, VEGFA, CAV1 and CDH1 were found to be key signaling and transcriptional regulators of these processes. Innate defense/immune responses were induced at later gestational ages (E18.5-20.5, STAT1, AP1, and EGFR being important regulators of these responses. Expression of RNAs associated with the cell cycle and chromatin assembly was repressed during prenatal lung maturation and was regulated by FOXM1, PLK1, chromobox, and high mobility group families of transcription factors. Strain dependent lung mRNA expression differences peaked at E18.5. At this time, mRNAs regulating surfactant and innate immunity were more abundantly expressed in lungs of B6 (short gestation than in A/J (long gestation mice, while expression of genes involved in chromatin assembly and histone modification were expressed at lower levels in B6 than in A/J mice. The present study systemically mapped key regulators

  19. Escherichia coli transcriptional regulatory network

    Directory of Open Access Journals (Sweden)

    Agustino Martinez-Antonio

    2011-06-01

    Full Text Available Escherichia coli is the most well-know bacterial model about the function of its molecular components. In this review are presented several structural and functional aspects of their transcriptional regulatory network constituted by transcription factors and target genes. The network discussed here represent to 1531 genes and 3421 regulatory interactions. This network shows a power-law distribution with a few global regulators and most of genes poorly connected. 176 of genes in the network correspond to transcription factors, which form a sub-network of seven hierarchical layers where global regulators tend to be set in superior layers while local regulators are located in the lower ones. There is a small set of proteins know as nucleoid-associated proteins, which are in a high cellular concentrations and reshape the nucleoid structure to influence the running of global transcriptional programs, to this mode of regulation is named analog regulation. Specific signal effectors assist the activity of most of transcription factors in E. coli. These effectors switch and tune the activity of transcription factors. To this type of regulation, depending of environmental signals is named the digital-precise-regulation. The integration of regulatory programs have place in the promoter region of transcription units where it is common to observe co-regulation among global and local TFs as well as of TFs sensing exogenous and endogenous conditions. The mechanistic logic to understand the harmonious operation of regulatory programs in the network should consider the globalism of TFs, their signal perceived, coregulation, genome position, and cellular concentration. Finally, duplicated TFs and their horizontal transfer influence the evolvability of members of the network. The most duplicated and transferred TFs are located in the network periphery.

  20. Roles within the Family

    Science.gov (United States)

    ... Life Listen Español Text Size Email Print Share Roles Within the Family Page Content Article Body Families ... family unit, and which rights, privileges, obligations, and roles are assigned to each family member. In most ...

  1. The transcription factor SOX17 is involved in the transcriptional control of the uteroglobin gene in rabbit endometrium.

    Science.gov (United States)

    Garcia, Carlos; Calvo, Enrique; Nieto, Antonio

    2007-10-15

    The transcription of the uteroglobin gene (ug) is induced by progesterone in the rabbit endometrium, primarily through the binding of the progesterone receptor to the distal region of the ug promoter. However, other transcription factors participate in the progesterone action. The proximal ug promoter contains several putative consensus sequences for the binding of various progesterone-dependent endometrial nuclear factors (Perez Martinez et al. [1996] Arch Biochem Biophys 333: 12-18), suggesting that several transcription factors might be implicated in the hormonal induction of ug. We report here that one of these progesterone-dependent factors specifically binds to the sequence CACAATG (-183/-177) of the rabbit ug promoter. This sequence (hereafter called element G') is very similar to the consensus sequence for binding of the SOX family of transcription factors. Mutation of the element G' reduced transcription from the ug promoter in transient expression experiments. The endometrial factor was purified and analyzed by nano-liquid chromatography and ion trap coupled mass spectrometry yielding two partial amino acid sequences corresponding to a region of SOX17 that is highly conserved inter-species. This identification was confirmed by immunological techniques using a specific anti-SOX17 antibody. In agreement with the above findings, overexpression of SOX17 in transfected endometrial cells increased transcription from the ug promoter. SOX17 gradually accumulated in the nucleus in vivo concomitant with the induction of ug expression by progesterone in the endometrium. Thus, these findings implicate, for the first time, SOX17 in the transcriptional control of rabbit ug.

  2. Integrating Family Resilience and Family Stress Theory.

    Science.gov (United States)

    Patterson, Joan M.

    2002-01-01

    The construct, family resilience, is defined differently by practitioners and researchers. This study tries to clarify the concept of family resilience. The foundation is family stress and coping theory, particularly the stress models that emphasize adaptation processes in families exposed to major adversities. (JDM)

  3. Structural basis of transcription initiation.

    Science.gov (United States)

    Zhang, Yu; Feng, Yu; Chatterjee, Sujoy; Tuske, Steve; Ho, Mary X; Arnold, Eddy; Ebright, Richard H

    2012-11-23

    During transcription initiation, RNA polymerase (RNAP) binds and unwinds promoter DNA to form an RNAP-promoter open complex. We have determined crystal structures at 2.9 and 3.0 Å resolution of functional transcription initiation complexes comprising Thermus thermophilus RNA polymerase, σ(A), and a promoter DNA fragment corresponding to the transcription bubble and downstream double-stranded DNA of the RNAP-promoter open complex. The structures show that σ recognizes the -10 element and discriminator element through interactions that include the unstacking and insertion into pockets of three DNA bases and that RNAP recognizes the -4/+2 region through interactions that include the unstacking and insertion into a pocket of the +2 base. The structures further show that interactions between σ and template-strand single-stranded DNA (ssDNA) preorganize template-strand ssDNA to engage the RNAP active center.

  4. Transcription factors - Methods and protocols

    Directory of Open Access Journals (Sweden)

    CarloAlberto Redi

    2011-03-01

    Full Text Available A hearty wellcome to prof. Higgins editorial toil: a necessary tool for those colleagues (young and older fighting each day with the transcription factor they are involved with. In fact, the book is a full coverage compendium of state of the art papers dealing with practical thecniques and theoretical concepts about transcription factors. Each of the chapters (twenty-four is written by colleagues already working with one of the many trascription factors we become acquainted with. For the sake of the reader the volume is divided in four parts: Part I is a brief (when compared to the others three ! introductory presentation of the shuttling (i.e., transcription factor nuclear-cytoplasmic trafficking achieved by three reviews presentation of this biologically critical phenomenon. Part II (nine chapters is devoted to the necessary techniques to study nuclear translocation ...............

  5. Pervasive transcription: detecting functional RNAs in bacteria.

    Science.gov (United States)

    Lybecker, Meghan; Bilusic, Ivana; Raghavan, Rahul

    2014-01-01

    Pervasive, or genome-wide, transcription has been reported in all domains of life. In bacteria, most pervasive transcription occurs antisense to protein-coding transcripts, although recently a new class of pervasive RNAs was identified that originates from within annotated genes. Initially considered to be non-functional transcriptional noise, pervasive transcription is increasingly being recognized as important in regulating gene expression. The function of pervasive transcription is an extensively debated question in the field of transcriptomics and regulatory RNA biology. Here, we highlight the most recent contributions addressing the purpose of pervasive transcription in bacteria and discuss their implications.

  6. NAC transcription factors in senescence

    DEFF Research Database (Denmark)

    Podzimska-Sroka, Dagmara; O'Shea, Charlotte; Gregersen, Per L.;

    2015-01-01

    Within the last decade, NAC transcription factors have been shown to play essential roles in senescence, which is the focus of this review. Transcriptome analyses associate approximately one third of Arabidopsis NAC genes and many crop NAC genes with senescence, thereby implicating NAC genes...... as important regulators of the senescence process. The consensus DNA binding site of the NAC domain is used to predict NAC target genes, and protein interaction sites can be predicted for the intrinsically disordered transcription regulatory domains of NAC proteins. The molecular characteristics...

  7. Subventricular zone microglia transcriptional networks.

    Science.gov (United States)

    Starossom, Sarah C; Imitola, Jaime; Wang, Yue; Cao, Li; Khoury, Samia J

    2011-07-01

    Microglia play an important role in inflammatory diseases of the central nervous system. There is evidence of microglial diversity with distinct phenotypes exhibiting either neuroprotection and repair or neurotoxicity. However the precise molecular mechanisms underlying this diversity are still unknown. Using a model of experimental autoimmune encephalomyelitis (EAE) we performed transcriptional profiling of isolated subventricular zone microglia from the acute and chronic disease phases of EAE. We found that microglia exhibit disease phase specific gene expression signatures, that correspond to unique gene ontology functions and genomic networks. Our data demonstrate for the first time, distinct transcriptional networks of microglia activation in vivo, that suggests a role as mediators of injury or repair.

  8. SSR markers in transcripts of genes linked to post-transcriptional and transcriptional regulatory functions during vegetative and reproductive development of Elaeis guineensis.

    Science.gov (United States)

    Tranbarger, Timothy John; Kluabmongkol, Wanwisa; Sangsrakru, Duangjai; Morcillo, Fabienne; Tregear, James W; Tragoonrung, Somvong; Billotte, Norbert

    2012-01-03

    The oil palm (Elaeis guineensis Jacq.) is a perennial monocotyledonous tropical crop species that is now the world's number one source of edible vegetable oil, and the richest dietary source of provitamin A. While new elite genotypes from traditional breeding programs provide steady yield increases, the long selection cycle (10-12 years) and the large areas required to cultivate oil palm make genetic improvement slow and labor intensive. Molecular breeding programs have the potential to make significant impacts on the rate of genetic improvement but the limited molecular resources, in particular the lack of molecular markers for agronomic traits of interest, restrict the application of molecular breeding schemes for oil palm. In the current study, 6,103 non-redundant ESTs derived from cDNA libraries of developing vegetative and reproductive tissues were annotated and searched for simple sequence repeats (SSRs). Primer pairs from sequences flanking 289 EST-SSRs were tested to detect polymorphisms in elite breeding parents and their crosses. 230 of these amplified PCR products, 88 of which were polymorphic within the breeding material tested. A detailed analysis and annotation of the EST-SSRs revealed the locations of the polymorphisms within the transcripts, and that the main functional category was related to transcription and post-transcriptional regulation. Indeed, SSR polymorphisms were found in sequences encoding AP2-like, bZIP, zinc finger, MADS-box, and NAC-like transcription factors in addition to other transcriptional regulatory proteins and several RNA interacting proteins. The identification of new EST-SSRs that detect polymorphisms in elite breeding material provides tools for molecular breeding strategies. The identification of SSRs within transcripts, in particular those that encode proteins involved in transcriptional and post-transcriptional regulation, will allow insight into the functional roles of these proteins by studying the phenotypic traits

  9. Insight into transcription factor gene duplication from Caenorhabditis elegans Promoterome-driven expression patterns

    Directory of Open Access Journals (Sweden)

    Vidal Marc

    2007-01-01

    Full Text Available Abstract Background The C. elegans Promoterome is a powerful resource for revealing the regulatory mechanisms by which transcription is controlled pan-genomically. Transcription factors will form the core of any systems biology model of genome control and therefore the promoter activity of Promoterome inserts for C. elegans transcription factor genes was examined, in vivo, with a reporter gene approach. Results Transgenic C. elegans strains were generated for 366 transcription factor promoter/gfp reporter gene fusions. GFP distributions were determined, and then summarized with reference to developmental stage and cell type. Reliability of these data was demonstrated by comparison to previously described gene product distributions. A detailed consideration of the results for one C. elegans transcription factor gene family, the Six family, comprising ceh-32, ceh-33, ceh-34 and unc-39 illustrates the value of these analyses. The high proportion of Promoterome reporter fusions that drove GFP expression, compared to previous studies, led to the hypothesis that transcription factor genes might be involved in local gene duplication events less frequently than other genes. Comparison of transcription factor genes of C. elegans and Caenorhabditis briggsae was therefore carried out and revealed very few examples of functional gene duplication since the divergence of these species for most, but not all, transcription factor gene families. Conclusion Examining reporter expression patterns for hundreds of promoters informs, and thereby improves, interpretation of this data type. Genes encoding transcription factors involved in intrinsic developmental control processes appear acutely sensitive to changes in gene dosage through local gene duplication, on an evolutionary time scale.

  10. Family Matters

    Directory of Open Access Journals (Sweden)

    Isabel de Riquer

    2011-04-01

    Full Text Available The scene is at the court of James I of Aragon in the mid-13th c., the place is the royal palace of Barcelona or any of the crown's other possessions, and the dramatis personae include the heir to the throne, prince Peire (future king Peire the Great, and the court's most famous troubadour, Cerverí de Girona (fl. 1259-85. Author of the largest corpus of any Occitan troubadour (114 poems, Cerverì distinguishes himself by the surprises and challenges he presents to his audience: an alba (the most openly erotic genre to the Virgin Mary, the Cobla in sis lengatges (Cobla in Six Languages, the apparently nonsensical Vers estrayn. Cerverì borrows equally from the folk-inspired Galician-Portuguese poetry and from the French tradition, including the chanson de malmariée, where a young woman bemoans being sold off by her family to an old man (gilos, "Jealous" and separated from her youthful doulz amis, some even praying for the death of their husband. Both within that tradition and among Cerverì's three chansons de malmariée, the Gelosesca stands out as "especially determined" to lose her husband, using every "solution" (prayer, black magic, potion or experimenta.

  11. A Comparative Study of RNA Polymerase II Transcription Machinery in Yeasts

    Science.gov (United States)

    Sharma, Nimisha; Mehta, Surbhi

    The control of gene expression, predominantly at the level of transcription, plays a fundamental role in biological processes determining the phenotypic changes in cells and organisms. The eukaryotes have evolved a complex and sophisticated transcription machinery to transcribe DNA into RNA. RNA polymerase II enzyme lies at the centre of the transcription apparatus that comprises nearly 60 polypeptides and is responsible for the expression and regulation of proteinencoding genes. Much of our present understanding and knowledge of the RNA polymerase II transcription apparatus in eukaryotes has been derived from studies in Saccharomyces cerevisiae. More recently, Schizosaccharomyces pombe has emerged as a better model system to study transcription because the transcription mechanism in this yeast is closer to that in higher eukaryotes. Also, studies on components of the basal transcription machinery have revealed a number of properties that are common with other eukaryotes, but have also highlighted some features unique to S. pombe. In fact, the fungal transcription associated protein families show greater species specificity and only 15% of these proteins contain homologues shared between both S. cerevisiae and S. pombe. In this chapter, we compare the RNA polymerase II transcription apparatus in different yeasts.

  12. The nuclear IκB family of proteins controls gene regulation and immune homeostasis.

    Science.gov (United States)

    MaruYama, Takashi

    2015-10-01

    The inhibitory IκB family of proteins is subdivided into two groups based on protein localization in the cytoplasm or in the nucleus. These proteins interact with NF-κB, a major transcription factor regulating the expression of many inflammatory cytokines, by modulating its transcriptional activity. However, nuclear IκB family proteins not only interact with NF-κB to change its transcriptional activity, but they also bind to chromatin and control gene expression. This review provides an overview of nuclear IκB family proteins and their role in immune homeostasis. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. The Hv NAC6 transcription factor: a positive regulator of penetration resistance in barley and Arabidopsis

    DEFF Research Database (Denmark)

    Jensen, Michael Krogh; Rung, Jesper Henrik; Gregersen, Per Langkjaer

    2007-01-01

    Pathogens induce the expression of many genes encoding plant transcription factors, though specific knowledge of the biological function of individual transcription factors remains scarce. NAC transcription factors are encoded in plants by a gene family with proposed functions in both abiotic...... and biotic stress adaptation, as well as in developmental processes. In this paper, we provide convincing evidence that a barley NAC transcription factor has a direct role in regulating basal defence. The gene transcript was isolated by differential display from barley leaves infected with the biotrophic...... powdery mildew fungus, Blumeria graminis f.sp. hordei (Bgh). The full-length cDNA clone was obtained using 5'-RACE and termed HvNAC6, due to its high similarity to the rice homologue, OsNAC6. Gene silencing of HvNAC6 during Bgh inoculation compromises penetration resistance in barley epidermal cells...

  14. The control of HIV transcription: keeping RNA polymerase II on track.

    Science.gov (United States)

    Ott, Melanie; Geyer, Matthias; Zhou, Qiang

    2011-11-17

    Thirteen years ago, human cyclin T1 was identified as part of the positive transcription elongation factor b (P-TEFb) and the long-sought host cofactor for the HIV-1 transactivator Tat. Recent years have brought new insights into the intricate regulation of P-TEFb function and its relationship with Tat, revealing novel mechanisms for controlling HIV transcription and fueling new efforts to overcome the barrier of transcriptional latency in eradicating HIV. Moreover, the improved understanding of HIV and Tat forms a basis for studying transcription elongation control in general. Here, we review advances in HIV transcription research with a focus on the growing family of cellular P-TEFb complexes, structural insights into the interactions between Tat, P-TEFb, and TAR RNA, and the multifaceted regulation of these interactions by posttranscriptional modifications of Tat. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. Transcriptional Crosstalk between Nuclear Receptors and Cytokine Signal Transduction Pathways in Immunity

    Institute of Scientific and Technical Information of China (English)

    Lihua Wang; Xiaohu Zhang; William L. Farrar; Xiaoyi Yang

    2004-01-01

    The nuclear receptor superfamily and the transcriptional factors associated with cytokines are inherently different families of signaling molecules and activate gene transcription by binding to their respective responsive element. However, it has become increasingly clear from our works and others that nuclear receptors are important regulators of cytokine production and function through complex and varied interactions between these distinct transcriptional factors. This review provides a general overview of the mechanism of action of nuclear receptors and their transcriptional crosstalk with transcriptional factors associated with cytokine transduction pathways. One of the most important mechanistic aspects is protein to protein interaction through a direct or co-regulator-mediated indirect manner. Such crosstalk is crucially involved in physiological and therapeutic roles of nuclear receptors and their ligands in immunity,inflammation and cytokine-related tumors. Cellular & Molecular Immunology. 2004;1(6):416-424.

  16. A Genome-Scale Resource for the Functional Characterization of Arabidopsis Transcription Factors

    Directory of Open Access Journals (Sweden)

    Jose L. Pruneda-Paz

    2014-07-01

    Full Text Available Extensive transcriptional networks play major roles in cellular and organismal functions. Transcript levels are in part determined by the combinatorial and overlapping functions of multiple transcription factors (TFs bound to gene promoters. Thus, TF-promoter interactions provide the basic molecular wiring of transcriptional regulatory networks. In plants, discovery of the functional roles of TFs is limited by an increased complexity of network circuitry due to a significant expansion of TF families. Here, we present the construction of a comprehensive collection of Arabidopsis TFs clones created to provide a versatile resource for uncovering TF biological functions. We leveraged this collection by implementing a high-throughput DNA binding assay and identified direct regulators of a key clock gene (CCA1 that provide molecular links between different signaling modules and the circadian clock. The resources introduced in this work will significantly contribute to a better understanding of the transcriptional regulatory landscape of plant genomes.

  17. The phylogeny of C/S1 bZIP transcription factors reveals a shared algal ancestry and the pre-angiosperm translational regulation of S1 transcripts

    NARCIS (Netherlands)

    Peviani, Alessia; Lastdrager, Jeroen; Hanson, Johannes; Snel, Berend

    2016-01-01

    Basic leucine zippers (bZIPs) form a large plant transcription factor family. C and S1 bZIP groups can heterodimerize, fulfilling crucial roles in seed development and stress response. S1 sequences also harbor a unique regulatory mechanism, termed Sucrose-Induced Repression of Translation (SIRT). Th

  18. Extensive chromatin remodelling and establishment of transcription factor 'hotspots' during early adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; John, Sam

    2011-01-01

    Adipogenesis is tightly controlled by a complex network of transcription factors acting at different stages of differentiation. Peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein (C/EBP) family members are key regulators of this process. We have employed DNase I...... and chromatin remodelling and is required for their establishment. Furthermore, a subset of early remodelled C/EBP-binding sites persists throughout differentiation and is later occupied by PPARγ, indicating that early C/EBP family members, in addition to their well-established role in activation of PPARγ...... transcription, may act as pioneering factors for PPARγ binding....

  19. Structural insights into transcription complexes

    NARCIS (Netherlands)

    Berger, I.; Blanco, A.G.; Boelens, R.; Cavarelli, J.; Coll, M.; Folkers, G.E.; Nie, Y.; Pogenberg, V.; Schultz, P.; Wilmanns, M.; Moras, D.; Poterszman, A.

    2011-01-01

    Control of transcription allows the regulation of cell activity in response to external stimuli and research in the field has greatly benefited from efforts in structural biology. In this review, based on specific examples from the European SPINE2-COMPLEXES initiative, we illustrate the impact of

  20. Transcription factor-based biosensor

    Science.gov (United States)

    Dietrich, Jeffrey A; Keasling, Jay D

    2013-10-08

    The present invention provides for a system comprising a BmoR transcription factor, a .sigma..sup.54-RNA polymerase, and a pBMO promoter operatively linked to a reporter gene, wherein the pBMO promoter is capable of expression of the reporter gene with an activated form of the BmoR and the .sigma..sup.54-RNA polymerase.

  1. Regulating transcription traffic around DSBs.

    Science.gov (United States)

    Plosky, Brian S

    2015-05-07

    If a double-strand break (DSB) occurs and either a DNA polymerase or RNA polymerase is coming along, how do we save the train? In this issue of Molecular Cell, Ui et al. (2015) describe a connection between an elongation factor and a repressive complex to prevent transcription in proximity to a DSB.

  2. HDG1 transcription factor targets

    NARCIS (Netherlands)

    Horstman, A.; Boutilier, K.A.; Sanchez Perez, Gabino

    2015-01-01

    The AIL transcription factor BABY BOOM (BBM) is required together with the related PLETHORA proteins for embryo and root meristem development and its expression is sufficient to confer pluripotency and totipotency to somatic tissues. We show that BBM and other AIL proteins interact with multiple

  3. Transcription factors in alkaloid biosynthesis.

    Science.gov (United States)

    Yamada, Yasuyuki; Sato, Fumihiko

    2013-01-01

    Higher plants produce a large variety of low-molecular weight secondary compounds. Among them, nitrogen-containing alkaloids are the most biologically active and are often used pharmaceutically. Whereas alkaloid chemistry has been intensively investigated, alkaloid biosynthesis, including the relevant biosynthetic enzymes, genes and their regulation, and especially transcription factors, is largely unknown, as only a limited number of plant species produce certain types of alkaloids and they are difficult to study. Recently, however, several groups have succeeded in isolating the transcription factors that are involved in the biosynthesis of several types of alkaloids, including bHLH, ERF, and WRKY. Most of them show Jasmonate (JA) responsiveness, which suggests that the JA signaling cascade plays an important role in alkaloid biosynthesis. Here, we summarize the types and functions of transcription factors that have been isolated in alkaloid biosynthesis, and characterize their similarities and differences compared to those in other secondary metabolite pathways, such as phenylpropanoid and terpenoid biosyntheses. The evolution of this biosynthetic pathway and regulatory network, as well as the application of these transcription factors to metabolic engineering, is discussed.

  4. Transcriptional networks in plant immunity.

    Science.gov (United States)

    Tsuda, Kenichi; Somssich, Imre E

    2015-05-01

    Next to numerous abiotic stresses, plants are constantly exposed to a variety of pathogens within their environment. Thus, their ability to survive and prosper during the course of evolution was strongly dependent on adapting efficient strategies to perceive and to respond to such potential threats. It is therefore not surprising that modern plants have a highly sophisticated immune repertoire consisting of diverse signal perception and intracellular signaling pathways. This signaling network is intricate and deeply interconnected, probably reflecting the diverse lifestyles and infection strategies used by the multitude of invading phytopathogens. Moreover it allows signal communication between developmental and defense programs thereby ensuring that plant growth and fitness are not significantly retarded. How plants integrate and prioritize the incoming signals and how this information is transduced to enable appropriate immune responses is currently a major research area. An important finding has been that pathogen-triggered cellular responses involve massive transcriptional reprogramming within the host. Additional key observations emerging from such studies are that transcription factors (TFs) are often sites of signal convergence and that signal-regulated TFs act in concert with other context-specific TFs and transcriptional co-regulators to establish sensory transcription regulatory networks required for plant immunity.

  5. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Directory of Open Access Journals (Sweden)

    Milka Martinez

    Full Text Available RUNX1 a member of the family of runt related transcription factors (RUNX, is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  6. Transcriptional Auto-Regulation of RUNX1 P1 Promoter.

    Science.gov (United States)

    Martinez, Milka; Hinojosa, Marcela; Trombly, Daniel; Morin, Violeta; Stein, Janet; Stein, Gary; Javed, Amjad; Gutierrez, Soraya E

    2016-01-01

    RUNX1 a member of the family of runt related transcription factors (RUNX), is essential for hematopoiesis. The expression of RUNX1 gene is controlled by two promoters; the distal P1 promoter and the proximal P2 promoter. Several isoforms of RUNX1 mRNA are generated through the use of both promoters and alternative splicing. These isoforms not only differs in their temporal expression pattern but also exhibit differences in tissue specificity. The RUNX1 isoforms derived from P2 are expressed in a variety of tissues, but expression of P1-derived isoform is restricted to cells of hematopoietic lineage. However, the control of hematopoietic-cell specific expression is poorly understood. Here we report regulation of P1-derived RUNX1 mRNA by RUNX1 protein. In silico analysis of P1 promoter revealed presence of two evolutionary conserved RUNX motifs, 0.6kb upstream of the transcription start site, and three RUNX motifs within 170bp of the 5'UTR. Transcriptional contribution of these RUNX motifs was studied in myeloid and T-cells. RUNX1 genomic fragment containing all sites show very low basal activity in both cell types. Mutation or deletion of RUNX motifs in the UTR enhances basal activity of the RUNX1 promoter. Chromatin immunoprecipitation revealed that RUNX1 protein is recruited to these sites. Overexpression of RUNX1 in non-hematopoietic cells results in a dose dependent activation of the RUNX1 P1 promoter. We also demonstrate that RUNX1 protein regulates transcription of endogenous RUNX1 mRNA in T-cell. Finally we show that SCL transcription factor is recruited to regions containing RUNX motifs in the promoter and the UTR and regulates activity of the RUNX1 P1 promoter in vitro. Thus, multiple lines of evidence show that RUNX1 protein regulates its own gene transcription.

  7. Role of Sam68 in Post-Transcriptional Gene Regulation

    Directory of Open Access Journals (Sweden)

    Flora Sánchez-Jiménez

    2013-11-01

    Full Text Available The STAR family of proteins links signaling pathways to various aspects of post-transcriptional regulation and processing of RNAs. Sam68 belongs to this class of heteronuclear ribonucleoprotein particle K (hnRNP K homology (KH single domain-containing family of RNA-binding proteins that also contains some domains predicted to bind critical components in signal transduction pathways. In response to phosphorylation and other post-transcriptional modifications, Sam68 has been shown to have the ability to link signal transduction pathways to downstream effects regulating RNA metabolism, including transcription, alternative splicing or RNA transport. In addition to its function as a docking protein in some signaling pathways, this prototypic STAR protein has been identified to have a nuclear localization and to take part in the formation of both nuclear and cytosolic multi-molecular complexes such as Sam68 nuclear bodies and stress granules. Coupling with other proteins and RNA targets, Sam68 may play a role in the regulation of differential expression and mRNA processing and translation according to internal and external signals, thus mediating important physiological functions, such as cell death, proliferation or cell differentiation.

  8. Stepwise mechanism for transcription fidelity

    Directory of Open Access Journals (Sweden)

    Zorov Savva

    2010-05-01

    Full Text Available Abstract Background Transcription is the first step of gene expression and is characterized by a high fidelity of RNA synthesis. During transcription, the RNA polymerase active centre discriminates against not just non-complementary ribo NTP substrates but also against complementary 2'- and 3'-deoxy NTPs. A flexible domain of the RNA polymerase active centre, the Trigger Loop, was shown to play an important role in this process, but the mechanisms of this participation remained elusive. Results Here we show that transcription fidelity is achieved through a multi-step process. The initial binding in the active centre is the major discrimination step for some non-complementary substrates, although for the rest of misincorporation events discrimination at this step is very poor. During the second step, non-complementary and 2'-deoxy NTPs are discriminated against based on differences in reaction transition state stabilization and partly in general base catalysis, for correct versus non-correct substrates. This step is determined by two residues of the Trigger Loop that participate in catalysis. In the following step, non-complementary and 2'-deoxy NTPs are actively removed from the active centre through a rearrangement of the Trigger Loop. The only step of discrimination against 3'-deoxy substrates, distinct from the ones above, is based on failure to orient the Trigger Loop catalytic residues in the absence of 3'OH. Conclusions We demonstrate that fidelity of transcription by multi-subunit RNA polymerases is achieved through a stepwise process. We show that individual steps contribute differently to discrimination against various erroneous substrates. We define the mechanisms and contributions of each of these steps to the overall fidelity of transcription.

  9. Crystal Structures of Two Transcriptional Regulators from Bacillus cereus Define the Conserved Structural Features of a PadR Subfamily

    NARCIS (Netherlands)

    Fibriansah, Guntur; Kovacs, Akos T.; Pool, Trijntje J.; Boonstra, Mirjam; Kuipers, Oscar P.; Thunnissen, Andy-Mark W. H.

    2012-01-01

    PadR-like transcriptional regulators form a structurally-related family of proteins that control the expression of genes associated with detoxification, virulence and multi-drug resistance in bacteria. Only a few members of this family have been studied by genetic, biochemical and biophysical method

  10. Family and family therapy in Russia.

    Science.gov (United States)

    Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

    2012-04-01

    This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized.

  11. Bequeathing Family Continuity.

    Science.gov (United States)

    Spanier, Graham B.

    1989-01-01

    Notes that many children who experience abuse, family disruption, or poverty reach adulthood with a strong commitment to family life. Questions whether changes in American families are indicators of pathology, deterioration, and instability; and asks how dysfunctional families transmit commitment to the concept of family to succeeding generations.…

  12. Family Reading Night

    Science.gov (United States)

    Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

    2007-01-01

    This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

  13. Transcriptional regulation of the human mitochondrial peptide deformylase (PDF).

    Science.gov (United States)

    Pereira-Castro, Isabel; Costa, Luís Teixeira da; Amorim, António; Azevedo, Luisa

    2012-05-18

    The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formyl-methionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. ATF-2 regulates lipopolysaccharide-induced transcription in macrophage cells.

    Science.gov (United States)

    Hirose, Noriyuki; Maekawa, Toshio; Shinagawa, Toshie; Ishii, Shunsuke

    2009-07-17

    The transcription factor ATF-2, a member of the ATF/CREB family, is a target of p38 that are involved in stress-induced apoptosis and in Toll-like receptor (TLR)-mediated signaling. Phosphorylation of ATF-2 at Thr-71 was enhanced by treating of RAW264.7 macrophage cells with either LPS, MALP-2, or CpG-ODN. LPS treatment enhanced the trans-activation capacity of ATF-2. Among multiple LPS-induced genes, the LPS-induced expression of Socs-3 was significantly reduced by the treatment of RAW264.7 cells with an Atf-2 siRNA. Transcription from the Socs-3 promoter was synergistically stimulated by ATF-2 and LPS, whereas it was suppressed by Atf-2 siRNA. Histone deacetylase 1 (HDAC1) interacted with ATF-2 after LPS treatment, but not before treatment. Treatment of RAW264.7 cells with trichostatin A, an inhibitor of HDAC, suppressed the LPS-induced Socs-3 expression, suggesting that HDAC1 positively regulates the LPS-induced transcription of Socs-3. Thus, ATF-2 plays an important role in TLR-mediated transcriptional control in macrophage cells.

  15. Transcriptional networks inferred from molecular signatures of breast cancer.

    Science.gov (United States)

    Tongbai, Ron; Idelman, Gila; Nordgard, Silje H; Cui, Wenwu; Jacobs, Jonathan L; Haggerty, Cynthia M; Chanock, Stephen J; Børresen-Dale, Anne-Lise; Livingston, Gary; Shaunessy, Patrick; Chiang, Chih-Hung; Kristensen, Vessela N; Bilke, Sven; Gardner, Kevin

    2008-02-01

    Global genomic approaches in cancer research have provided new and innovative strategies for the identification of signatures that differentiate various types of human cancers. Computational analysis of the promoter composition of the genes within these signatures may provide a powerful method for deducing the regulatory transcriptional networks that mediate their collective function. In this study we have systematically analyzed the promoter composition of gene classes derived from previously established genetic signatures that recently have been shown to reliably and reproducibly distinguish five molecular subtypes of breast cancer associated with distinct clinical outcomes. Inferences made from the trends of transcription factor binding site enrichment in the promoters of these gene groups led to the identification of regulatory pathways that implicate discrete transcriptional networks associated with specific molecular subtypes of breast cancer. One of these inferred pathways predicted a role for nuclear factor-kappaB in a novel feed-forward, self-amplifying, autoregulatory module regulated by the ERBB family of growth factor receptors. The existence of this pathway was verified in vivo by chromatin immunoprecipitation and shown to be deregulated in breast cancer cells overexpressing ERBB2. This analysis indicates that approaches of this type can provide unique insights into the differential regulatory molecular programs associated with breast cancer and will aid in identifying specific transcriptional networks and pathways as potential targets for tumor subtype-specific therapeutic intervention.

  16. MRTF potentiates TEAD-YAP transcriptional activity causing metastasis.

    Science.gov (United States)

    Kim, Tackhoon; Hwang, Daehee; Lee, Dahye; Kim, Jeong-Hwan; Kim, Seon-Young; Lim, Dae-Sik

    2017-02-15

    Yes-associated protein (YAP) and myocardin-related transcription factor (MRTF) play similar roles and exhibit significant crosstalk in directing transcriptional responses to chemical and physical extracellular cues. The mechanism underlying this crosstalk, however, remains unclear. Here, we show MRTF family proteins bind YAP via a conserved PPXY motif that interacts with the YAP WW domain. This interaction allows MRTF to recruit NcoA3 to the TEAD-YAP transcriptional complex and potentiate its transcriptional activity. We show this interaction of MRTF and YAP is critical for LPA-induced cancer cell invasion in vitro and breast cancer metastasis to the lung in vivo We also demonstrate the significance of MRTF-YAP binding in regulation of YAP activity upon acute actin cytoskeletal damage. Acute actin disruption induces nucleo-cytoplasmic shuttling of MRTF, and this process underlies the LATS-independent regulation of YAP activity. Our results provide clear evidence of crosstalk between MRTF and YAP independent of the LATS kinases that normally act upstream of YAP signaling. Our results also suggest a mechanism by which extracellular stimuli can coordinate physiological events downstream of YAP. © 2016 The Authors.

  17. The Chd Family of Chromatin Remodelers

    OpenAIRE

    Marfella, Concetta G.A.; Imbalzano, Anthony N.

    2007-01-01

    Chromatin remodeling enzymes contribute to the dynamic changes that occur in chromatin structure during cellular processes such as transcription, recombination, repair, and replication. Members of the chromodomain helicase DNA-binding (Chd) family of enzymes belong to the SNF2 superfamily of ATP-dependent chromatin remodelers. The Chd proteins are distinguished by the presence of two N-terminal chromodomains that function as interaction surfaces for a variety of chromatin components. Genetic,...

  18. Family Factors in Small Family Business Growth

    National Research Council Canada - National Science Library

    Jim Cater; Marilyn Young

    2016-01-01

    .... We suggest that while all three patterns of small family business growth may lead to individual company success and sustainability, businesses with units in multiple trade areas may be most adept at managing the six family factors.

  19. Investigating transcription reinitiation through in vitro approaches.

    Science.gov (United States)

    Dieci, Giorgio; Fermi, Beatrice; Bosio, Maria Cristina

    2014-01-01

    By influencing the number of RNA molecules repeatedly synthesized from the same gene, the control of transcription reinitiation has the potential to shape the transcriptome. Transcription reinitiation mechanisms have been mainly addressed in vitro, through approaches based on both crude and reconstituted systems. These studies support the notion that transcription reinitiation and its regulation rely on dedicated networks of molecular interactions within transcription machineries. At the same time, comparison with in vivo transcription rates suggests that additional mechanisms, factors and conditions must exist in the nucleus, whose biochemical elucidation is a fascinating challenge for future in vitro transcription studies.

  20. The study on the role of transcription factor GATA binding protein 3 in familial Alzheimer's disease pathogenesis%转录因子GATA结合蛋白3在家族性阿尔茨海默病发病机制中的作用

    Institute of Scientific and Technical Information of China (English)

    秦伟; 周爱红; 左秀美; 王芬; 程哲; 贾建平

    2011-01-01

    Objective To investigate the mechanisms of decreasing insulin degrading enzyme (IDE) level by mutation V97L in the gene presenilin 1 (PS-1).Methods Transcription factor GATA binding protein 3 (GATA-3) activity was assessed by protein/DNA array and verified by Western blot in SH-SY5Y cells transfected by PS-1 mutation V97L.Results Protein/DNA array and Western blot revealed that there was increased transcript factor activity (5.5 times high) and protein level of GATA-3 in V97L-PS-1 transfected SH-SY5Y cells.Transcription factor GATA-3 can bind to the IDE promoter and negatively control the IDE transcription level.Conclusion PS-1 mutation V97L may regulate the transcription of IDE via GATA-3, and subsequently involve in deposition of Aβ42 and development of Alzheimer's disease.%目的 探讨家族性阿尔茨海默病(Alzheimer's disease,AD)相关的早老素1(presenilin-1,PS-1)V97L突变引起胰岛素降解酶(insulin degrading enzyme,IDE)降低的机制.方法 应用转录因子活性芯片技术检测转录因子活性的差异,再用Western b1ot法验证芯片结果.结果 芯片结合MatInspector软件分析发现,上调了5.5倍的转录因子GATA结合蛋白3(GATA binding protein 3,GATA-3)在IDE启动子上有结合位点,并对IDE起负性调控作用.Westem b1ot也证实稳定转染PS-1 V97L细胞系中GATA-3蛋白表达明显增高.结论 PS-1 V97L突变可能通过上调转录因子GATA-3抑制IDE的表达,影响β-淀粉样蛋白42含量进而参与AD的发生.