WorldWideScience

Sample records for hypercondensed chromatin architecture

  1. A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

    KAUST Repository

    Jé gu, Teddy; Domenichini, Sé verine; Blein, Thomas; Ariel, Federico; Christ, Auré lie; Kim, SoonKap; Crespi, Martin; Boutet-Mercey, Sté phanie; Mouille, Gré gory; Bourge, Mickaë l; Hirt, Heribert; Bergounioux, Catherine; Raynaud, Cé cile; Benhamed, Moussa

    2015-01-01

    Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

  2. A SWI/SNF Chromatin Remodelling Protein Controls Cytokinin Production through the Regulation of Chromatin Architecture

    KAUST Repository

    Jégu, Teddy

    2015-10-12

    Chromatin architecture determines transcriptional accessibility to DNA and consequently gene expression levels in response to developmental and environmental stimuli. Recently, chromatin remodelers such as SWI/SNF complexes have been recognized as key regulators of chromatin architecture. To gain insight into the function of these complexes during root development, we have analyzed Arabidopsis knock-down lines for one sub-unit of SWI/SNF complexes: BAF60. Here, we show that BAF60 is a positive regulator of root development and cell cycle progression in the root meristem via its ability to down-regulate cytokinin production. By opposing both the deposition of active histone marks and the formation of a chromatin regulatory loop, BAF60 negatively regulates two crucial target genes for cytokinin biosynthesis (IPT3 and IPT7) and one cell cycle inhibitor (KRP7). Our results demonstrate that SWI/SNF complexes containing BAF60 are key factors governing the equilibrium between formation and dissociation of a chromatin loop controlling phytohormone production and cell cycle progression.

  3. Transcriptional decomposition reveals active chromatin architectures and cell specific regulatory interactions

    DEFF Research Database (Denmark)

    Rennie, Sarah; Dalby, Maria; van Duin, Lucas

    2018-01-01

    Transcriptional regulation is tightly coupled with chromosomal positioning and three-dimensional chromatin architecture. However, it is unclear what proportion of transcriptional activity is reflecting such organisation, how much can be informed by RNA expression alone and how this impacts disease...... proportion of total levels and is highly informative of topological associating domain activities and organisation, revealing boundaries and chromatin compartments. Furthermore, expression data alone accurately predict individual enhancer-promoter interactions, drawing features from expression strength...... between transcription and chromatin architecture....

  4. Chromatin architecture and gene expression in Escherichia coli

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Ussery, David

    2004-01-01

    Two recent genome-scale analyses underscore the importance of DNA topology and chromatin structure in regulating transcription in Escherichia coli.......Two recent genome-scale analyses underscore the importance of DNA topology and chromatin structure in regulating transcription in Escherichia coli....

  5. Retroviruses Hijack Chromatin Loops to Drive Oncogene Expression and Highlight the Chromatin Architecture around Proto-Oncogenic Loci

    Science.gov (United States)

    Pattison, Jillian M.; Wright, Jason B.; Cole, Michael D.

    2015-01-01

    The majority of the genome consists of intergenic and non-coding DNA sequences shown to play a major role in different gene regulatory networks. However, the specific potency of these distal elements as well as how these regions exert function across large genomic distances remains unclear. To address these unresolved issues, we closely examined the chromatin architecture around proto-oncogenic loci in the mouse and human genomes to demonstrate a functional role for chromatin looping in distal gene regulation. Using cell culture models, we show that tumorigenic retroviral integration sites within the mouse genome occur near existing large chromatin loops and that this chromatin architecture is maintained within the human genome as well. Significantly, as mutagenesis screens are not feasible in humans, we demonstrate a way to leverage existing screens in mice to identify disease relevant human enhancers and expose novel disease mechanisms. For instance, we characterize the epigenetic landscape upstream of the human Cyclin D1 locus to find multiple distal interactions that contribute to the complex cis-regulation of this cell cycle gene. Furthermore, we characterize a novel distal interaction upstream of the Cyclin D1 gene which provides mechanistic evidence for the abundant overexpression of Cyclin D1 occurring in multiple myeloma cells harboring a pathogenic translocation event. Through use of mapped retroviral integrations and translocation breakpoints, our studies highlight the importance of chromatin looping in oncogene expression, elucidate the epigenetic mechanisms crucial for distal cis-regulation, and in one particular instance, explain how a translocation event drives tumorigenesis through upregulation of a proto-oncogene. PMID:25799187

  6. Chromatin structure and dynamics in hot environments: architectural proteins and DNA topoisomerases of thermophilic archaea.

    Science.gov (United States)

    Visone, Valeria; Vettone, Antonella; Serpe, Mario; Valenti, Anna; Perugino, Giuseppe; Rossi, Mosè; Ciaramella, Maria

    2014-09-25

    In all organisms of the three living domains (Bacteria, Archaea, Eucarya) chromosome-associated proteins play a key role in genome functional organization. They not only compact and shape the genome structure, but also regulate its dynamics, which is essential to allow complex genome functions. Elucidation of chromatin composition and regulation is a critical issue in biology, because of the intimate connection of chromatin with all the essential information processes (transcription, replication, recombination, and repair). Chromatin proteins include architectural proteins and DNA topoisomerases, which regulate genome structure and remodelling at two hierarchical levels. This review is focussed on architectural proteins and topoisomerases from hyperthermophilic Archaea. In these organisms, which live at high environmental temperature (>80 °C <113 °C), chromatin proteins and modulation of the DNA secondary structure are concerned with the problem of DNA stabilization against heat denaturation while maintaining its metabolic activity.

  7. Chromatin Structure and Dynamics in Hot Environments: Architectural Proteins and DNA Topoisomerases of Thermophilic Archaea

    Directory of Open Access Journals (Sweden)

    Valeria Visone

    2014-09-01

    Full Text Available In all organisms of the three living domains (Bacteria, Archaea, Eucarya chromosome-associated proteins play a key role in genome functional organization. They not only compact and shape the genome structure, but also regulate its dynamics, which is essential to allow complex genome functions. Elucidation of chromatin composition and regulation is a critical issue in biology, because of the intimate connection of chromatin with all the essential information processes (transcription, replication, recombination, and repair. Chromatin proteins include architectural proteins and DNA topoisomerases, which regulate genome structure and remodelling at two hierarchical levels. This review is focussed on architectural proteins and topoisomerases from hyperthermophilic Archaea. In these organisms, which live at high environmental temperature (>80 °C <113 °C, chromatin proteins and modulation of the DNA secondary structure are concerned with the problem of DNA stabilization against heat denaturation while maintaining its metabolic activity.

  8. ERECTA signaling controls Arabidopsis inflorescence architecture through chromatin-mediated activation of PRE1 expression.

    Science.gov (United States)

    Cai, Hanyang; Zhao, Lihua; Wang, Lulu; Zhang, Man; Su, Zhenxia; Cheng, Yan; Zhao, Heming; Qin, Yuan

    2017-06-01

    Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied. Comparative transcriptome analysis was applied to identify downstream components. Chromatin immunoprecipitation and nucleosome occupancy was further investigated. The results indicated that the chromatin remodeler SWR1 coordinates with ERECTA signaling in regulating inflorescence architecture by activating the expression of PRE1 family genes and promoting pedicel elongation. It was found that SWR1 is required for the incorporation of the H2A.Z histone variant into nucleosomes of the whole PRE1 gene family and the ERECTA controlled expression of PRE1 gene family through regulating nucleosome dynamics. We propose that utilization of a chromatin remodeling complex to regulate gene expression is a common theme in developmental control across kingdoms. These findings shed light on the mechanisms through which chromatin remodelers orchestrate complex transcriptional regulation of gene expression in coordination with a developmental cue. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Chromatin architecture: A new dimension in the dynamic control of gene expression

    KAUST Repository

    Ramirez Prado, Juan Sebastian; Rodriguez-Granados, Natalia Yaneth; Ariel, Federico; Raynaud, Cé cile; Benhamed, Moussa

    2016-01-01

    As the most recent evidence of eukaryotic cell complexity, genome architecture has astounded the scientific community and prompted a variety of technical and cognitive challenges. Several technologies have emerged and evidenced the integration of chromatin packaging and topology, epigenetic processes, and transcription for the pertinent regulation of gene expression. In the present addendum we present and discuss some of our recent research, directed toward the holistic comprehension of the processes by which plants respond to environmental and developmental stimuli. We propose that the study of genome topology and genomic interactions is essential for the understanding of the molecular mechanisms behind a phenotype. Even though our knowledge and understanding of genome architecture and hierarchy has improved substantially in the last few years -in Arabidopsis and other eukaryotes -, there is still a long way ahead in this relatively new field of study. For this, it is necessary to take advantage of the high resolution of the emerging available techniques, and perform integrative approaches with which it will be possible to depict the role of chromatin architecture in the regulation of transcription and ultimately, physiological processes.

  10. Chromatin architecture: A new dimension in the dynamic control of gene expression

    KAUST Repository

    Ramirez Prado, Juan Sebastian

    2016-09-10

    As the most recent evidence of eukaryotic cell complexity, genome architecture has astounded the scientific community and prompted a variety of technical and cognitive challenges. Several technologies have emerged and evidenced the integration of chromatin packaging and topology, epigenetic processes, and transcription for the pertinent regulation of gene expression. In the present addendum we present and discuss some of our recent research, directed toward the holistic comprehension of the processes by which plants respond to environmental and developmental stimuli. We propose that the study of genome topology and genomic interactions is essential for the understanding of the molecular mechanisms behind a phenotype. Even though our knowledge and understanding of genome architecture and hierarchy has improved substantially in the last few years -in Arabidopsis and other eukaryotes -, there is still a long way ahead in this relatively new field of study. For this, it is necessary to take advantage of the high resolution of the emerging available techniques, and perform integrative approaches with which it will be possible to depict the role of chromatin architecture in the regulation of transcription and ultimately, physiological processes.

  11. Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation

    Energy Technology Data Exchange (ETDEWEB)

    Popova, Evgenya Y.; Krauss, Sharon Wald; Short, Sarah A.; Lee, Gloria; Villalobos, Jonathan; Etzell, Joan; Koury, Mark J.; Ney, Paul A.; Chasis, Joel Anne; Grigoryev, Sergei A.

    2008-08-21

    Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, chromatin condensation and, in mammals, culminates in nuclear extrusion. To date, although mechanisms regulating avian erythroid chromatin condensation have been identified, little is known regarding this process during mammalian erythropoiesis. To elucidate the molecular basis for mammalian erythroblast chromatin condensation, we used Friend virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage erythroblasts had similar levels of linker and core histones, only a slight difference in nucleosome repeats, and no significant accumulation of known developmentally-regulated architectural chromatin proteins. However, histone H3(K9) dimethylation markedly increased while histone H4(K12) acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed. One histone deacetylase, HDAC5, was significantly upregulated during the terminal stages of Friend virus-infected erythroblast differentiation. Treatment with histone deacetylase inhibitor, trichostatin A, blocked both chromatin condensation and nuclear extrusion. Based on our data, we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentally-regulated architectural proteins in nucleated blood cells.

  12. Chromatin-mediated transcriptional regulation by the yeast architectural factors NHP6A and NHP6B

    DEFF Research Database (Denmark)

    Moreira, José Manuel Alfonso; Holmberg, S

    2000-01-01

    The Saccharomyces cerevisiae NHP6A and NHP6B proteins are chromatin architectural factors, functionally and structurally related to the mammalian high mobility group (HMG)-1 and -2 proteins, a family of non-sequence-specific DNA binding proteins. nhp6a nhp6b mutants have various morphological...

  13. MRN1 implicates chromatin remodeling complexes and architectural factors in mRNA maturation

    DEFF Research Database (Denmark)

    Düring, Louis; Thorsen, Michael; Petersen, Darima

    2012-01-01

    A functional relationship between chromatin structure and mRNA processing events has been suggested, however, so far only a few involved factors have been characterized. Here we show that rsc nhp6¿¿ mutants, deficient for the function of the chromatin remodeling factor RSC and the chromatin....... Genetic interactions are observed between 2 µm-MRN1 and the splicing deficient mutants snt309¿, prp3, prp4, and prp22, and additional genetic analyses link MRN1, SNT309, NHP6A/B, SWI/SNF, and RSC supporting the notion of a role of chromatin structure in mRNA processing....

  14. The detailed 3D multi-loop aggregate/rosette chromatin architecture and functional dynamic organization of the human and mouse genomes

    DEFF Research Database (Denmark)

    Knoch, Tobias A; Wachsmuth, Malte; Kepper, Nick

    2016-01-01

    BACKGROUND: The dynamic three-dimensional chromatin architecture of genomes and its co-evolutionary connection to its function-the storage, expression, and replication of genetic information-is still one of the central issues in biology. Here, we describe the much debated 3D architecture...... of the human and mouse genomes from the nucleosomal to the megabase pair level by a novel approach combining selective high-throughput high-resolution chromosomal interaction capture (T2C), polymer simulations, and scaling analysis of the 3D architecture and the DNA sequence. RESULTS: The genome is compacted...... into a chromatin quasi-fibre with ~5 ± 1 nucleosomes/11 nm, folded into stable ~30-100 kbp loops forming stable loop aggregates/rosettes connected by similar sized linkers. Minor but significant variations in the architecture are seen between cell types and functional states. The architecture and the DNA sequence...

  15. Polymer physics predicts the effects of structural variants on chromatin architecture.

    Science.gov (United States)

    Bianco, Simona; Lupiáñez, Darío G; Chiariello, Andrea M; Annunziatella, Carlo; Kraft, Katerina; Schöpflin, Robert; Wittler, Lars; Andrey, Guillaume; Vingron, Martin; Pombo, Ana; Mundlos, Stefan; Nicodemi, Mario

    2018-05-01

    Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and cause disease. However, the prediction of such effects remains a challenge. Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs.

  16. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription.

    Science.gov (United States)

    Lai, Fan; Orom, Ulf A; Cesaroni, Matteo; Beringer, Malte; Taatjes, Dylan J; Blobel, Gerd A; Shiekhattar, Ramin

    2013-02-28

    Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms. Although the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X-chromosome inactivation and imprinting, different classes of lncRNAs may have varied biological functions. We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their neighbouring genes using a cis-mediated mechanism. To define the precise mode by which such enhancer-like RNAs function, we depleted factors with known roles in transcriptional activation and assessed their role in RNA-dependent activation. Here we report that depletion of the components of the co-activator complex, Mediator, specifically and potently diminished the ncRNA-induced activation of transcription in a heterologous reporter assay using human HEK293 cells. In vivo, Mediator is recruited to ncRNA-a target genes and regulates their expression. We show that ncRNA-a interact with Mediator to regulate its chromatin localization and kinase activity towards histone H3 serine 10. The Mediator complex harbouring disease- displays diminished ability to associate with activating ncRNAs. Chromosome conformation capture confirmed the presence of DNA looping between the ncRNA-a loci and its targets. Importantly, depletion of Mediator subunits or ncRNA-a reduced the chromatin looping between the two loci. Our results identify the human Mediator complex as the transducer of activating ncRNAs and highlight the importance of Mediator and activating ncRNA association in human disease.

  17. Suberoylanilide Hydroxyamic Acid Modification of Chromatin Architecture Affects DNA Break Formation and Repair

    International Nuclear Information System (INIS)

    Singh, Sheetal; Le Hongan; Shih, S.-J.; Ho, Bay; Vaughan, Andrew T.

    2010-01-01

    Purpose: Chromatin-modifying compounds that inhibit the activity of histone deacetylases have shown potency as radiosensitizers, but the action of these drugs at a molecular level is not clear. Here we investigated the effect of suberoylanilide hydroxyamic acid (SAHA) on DNA breaks and their repair and induction of rearrangements. Methods and Materials: The effect of SAHA on both clonogenic survival and repair was assessed using cell lines SCC-25, MCF7, and TK6. In order to study unique DNA double-strand breaks, anti-CD95 antibody was employed to introduce a DNA double-strand break at a known location within the 11q23 region. The effects of SAHA on DNA cleavage and rearrangements were analyzed by ligation-mediated PCR and inverse PCR, respectively. Results: SAHA acts as radiosensitizer at 1 μM, with dose enhancement factors (DEFs) at 10% survival of: SCC-25 - 1.24 ± 0.05; MCF7 - 1.16 ± 0.09 and TK6 - 1.17 ± 0.05, and it reduced the capacity of SCC-25 cells to repair radiation induced lesions. Additionally, SAHA treatment diffused site-specific fragmentation over at least 1 kbp in TK6 cells. Chromosomal rearrangements produced in TK6 cells exposed to SAHA showed a reduction in microhomology at the breakpoint between 11q23 and partner chromosomes. Conclusions: SAHA shows efficacy as a radiosensitizer at clinically obtainable levels. In its presence, targeted DNA strand breaks occur over an expanded region, indicating increased chromatin access. The rejoining of such breaks is degraded by SAHA when measured as rearrangements at the molecular level and rejoining that contributes to cell survival.

  18. High-order chromatin architecture shapes the landscape of chromosomal alterations in cancer

    Science.gov (United States)

    Fudenberg, Geoffrey; Getz, Gad; Meyerson, Matthew; Mirny, Leonid

    2012-02-01

    The rapid growth of cancer genome structural information provides an opportunity for a better understanding of the mutational mechanisms of genomic alterations in cancer and the forces of selection that act upon them. Here we test the evidence for two major forces, spatial chromosome structure and purifying (or negative) selection, that shape the landscape of somatic copy-number alterations (SCNAs) in cancer (Beroukhim et al, 2010). Using a maximum likelihood framework we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule (FG) model (Lieberman-Aiden and Van Berkum et al, 2009). This analysis provides evidence that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and additionally suggests that purifying selection as well as positive selection shapes the landscape of SCNAs during somatic evolution of cancer cells.

  19. Chromatin meets its organizers.

    Science.gov (United States)

    Bodnar, Megan S; Spector, David L

    2013-06-06

    Chromatin organization and gene-gene interactions are critical components of carrying out developmental programs. Phillips-Cremins et al. identify a series of unexpected architectural proteins that work in a combinatorial manner to functionally organize chromatin in a cell-type-specific manner at the submegabase-length scale. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Combinatorial depletion analysis to assemble the network architecture of the SAGA and ADA chromatin remodeling complexes.

    Science.gov (United States)

    Lee, Kenneth K; Sardiu, Mihaela E; Swanson, Selene K; Gilmore, Joshua M; Torok, Michael; Grant, Patrick A; Florens, Laurence; Workman, Jerry L; Washburn, Michael P

    2011-07-05

    Despite the availability of several large-scale proteomics studies aiming to identify protein interactions on a global scale, little is known about how proteins interact and are organized within macromolecular complexes. Here, we describe a technique that consists of a combination of biochemistry approaches, quantitative proteomics and computational methods using wild-type and deletion strains to investigate the organization of proteins within macromolecular protein complexes. We applied this technique to determine the organization of two well-studied complexes, Spt-Ada-Gcn5 histone acetyltransferase (SAGA) and ADA, for which no comprehensive high-resolution structures exist. This approach revealed that SAGA/ADA is composed of five distinct functional modules, which can persist separately. Furthermore, we identified a novel subunit of the ADA complex, termed Ahc2, and characterized Sgf29 as an ADA family protein present in all Gcn5 histone acetyltransferase complexes. Finally, we propose a model for the architecture of the SAGA and ADA complexes, which predicts novel functional associations within the SAGA complex and provides mechanistic insights into phenotypical observations in SAGA mutants.

  1. Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells.

    Science.gov (United States)

    Glinsky, Gennadi V

    2018-03-01

    Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL, hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331 of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs within specific TADs by inserting novel and/or erasing existing non-coding regulatory sequences. Consequently, markedly distinct features of the principal regulatory structures of interphase chromatin evolved in the hESC genome compared to mouse: the SED quantity is 3-fold higher and the median SED size is significantly larger. Concomitantly, the overall TAD quantity is increased by 42% while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC genome. Present analyses illustrate a putative global role for transposable elements and HSGRL in shaping the human-specific features of the interphase chromatin organization and functions, which are facilitated by accelerated creation of novel transcription factor binding sites and new enhancers driven by targeted placement of HSGRL at defined genomic coordinates. A trend toward the convergence of TAD and SED architectures of interphase chromatin in the hESC genome may reflect changes of 3D-folding patterns of linear chromatin fibers designed to enhance both

  2. Reprogramming chromatin

    DEFF Research Database (Denmark)

    Ehrensberger, Andreas Hasso; Svejstrup, Jesper Qualmann

    2012-01-01

    attributed to high kinetic barriers that affect all cells equally and can only be overcome by rare stochastic events. The barriers to reprogramming are likely to involve transformations of chromatin state because (i) inhibitors of chromatin-modifying enzymes can enhance the efficiency of reprogramming...... and (ii) knockdown or knock-out of chromatin-modifying enzymes can lower the efficiency of reprogramming. Here, we review the relationship between chromatin state transformations (chromatin reprogramming) and cellular reprogramming, with an emphasis on transcription factors, chromatin remodeling factors...

  3. H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

    Directory of Open Access Journals (Sweden)

    Shieh Grace S

    2011-12-01

    Full Text Available Abstract Background The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA. Results Here we provide evidence that H2B monoubiquitylation (H2BK123ub1 marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3, which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality. Conclusion These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.

  4. H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

    LENUS (Irish Health Repository)

    Shieh, Grace S.

    2011-12-22

    Abstract Background The packaging of DNA into chromatin regulates transcription from initiation through 3\\' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA. Results Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in Saccharomyces cerevisiae. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an htb-K123R mutation, leads to synthetic lethality. Conclusion These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.

  5. Morphological changes of nuclear and chromatin architecture after microwave electromagnetic field exposure in 3T3 fibroblast cell cultures

    International Nuclear Information System (INIS)

    Mircea, D.; Chirila, Lavinia; Ciurea, A. V.; Helm, G.; Hankins, G.; Redrick, Jan; Gavrila, L.; Sheppard, B.; Bloodgoog, R.; Pallin, I.; Nitu, Rozalia; Rusu, I.

    2001-01-01

    It is already demonstrated in the literature that electromagnetic fields, particularly the microwave irradiation could be a powerful weapon against human tumors , but also against human body itself, depending on the wave parameters and irradiation time. The effects of microwave electromagnetic fields on living systems were studied in detail all over the world and, furthermore, the potential of intracellular damages by cytoskeleton, nuclear, chromatin and DNA alterations were carefully evaluated. In this study, the authors emphasize the morphological changes of nucleus and chromatin in fibroblast cell line 3T3 after microwave exposure with progressive increasing powers and times of irradiation. It was used a pulsed wave with 915 MHz frequency, with forward power ranging between 3 - 10 W, emitted by a helical microwave antenna placed into the cell culture medium, close to the cell monolayer. The authors tried to define certain severity stages of nuclear material alterations following different wave intensities and to compare these effects with other cytoplasmic organelle alterations. It was found that the nuclear material is the most sensitive intracellular structure in microwave electromagnetic field exposure. Also the authors tried to establish a well-defined protocol of irradiation with microwave electromagnetic fields in order to destroy the microtubule system of cytoskeleton in different types of cellular lines, in vitro. The cytoskeleton structure was evaluated by immunofluorescence methods. In non-muscle cells the cytoskeleton stability is achieved by interaction between microtubule system and actin filaments. Microtubule depolymerization by microwave exposure produces a secondary instability of cytoskeleton, the actin filaments coupling and cell contractility. The increasing of fibroblast contractility allows a more efficient treatment of the wounds with low spontaneous healing. Electromagnetic therapy could be an alternative therapy in plastic surgery

  6. Chromatin Hydrodynamics

    Science.gov (United States)

    Bruinsma, Robijn; Grosberg, Alexander Y.; Rabin, Yitzhak; Zidovska, Alexandra

    2014-01-01

    Following recent observations of large scale correlated motion of chromatin inside the nuclei of live differentiated cells, we present a hydrodynamic theory—the two-fluid model—in which the content of a nucleus is described as a chromatin solution with the nucleoplasm playing the role of the solvent and the chromatin fiber that of a solute. This system is subject to both passive thermal fluctuations and active scalar and vector events that are associated with free energy consumption, such as ATP hydrolysis. Scalar events drive the longitudinal viscoelastic modes (where the chromatin fiber moves relative to the solvent) while vector events generate the transverse modes (where the chromatin fiber moves together with the solvent). Using linear response methods, we derive explicit expressions for the response functions that connect the chromatin density and velocity correlation functions to the corresponding correlation functions of the active sources and the complex viscoelastic moduli of the chromatin solution. We then derive general expressions for the flow spectral density of the chromatin velocity field. We use the theory to analyze experimental results recently obtained by one of the present authors and her co-workers. We find that the time dependence of the experimental data for both native and ATP-depleted chromatin can be well-fitted using a simple model—the Maxwell fluid—for the complex modulus, although there is some discrepancy in terms of the wavevector dependence. Thermal fluctuations of ATP-depleted cells are predominantly longitudinal. ATP-active cells exhibit intense transverse long wavelength velocity fluctuations driven by force dipoles. Fluctuations with wavenumbers larger than a few inverse microns are dominated by concentration fluctuations with the same spectrum as thermal fluctuations but with increased intensity. PMID:24806919

  7. Modulation of Higher Order Chromatin Conformation in Mammalian Cell Nuclei Can Be Mediated by Polyamines and Divalent Cations.

    Directory of Open Access Journals (Sweden)

    Ashwat Visvanathan

    Full Text Available The organisation of the large volume of mammalian genomic DNA within cell nuclei requires mechanisms to regulate chromatin compaction involving the reversible formation of higher order structures. The compaction state of chromatin varies between interphase and mitosis and is also subject to rapid and reversible change upon ATP depletion/repletion. In this study we have investigated mechanisms that may be involved in promoting the hyper-condensation of chromatin when ATP levels are depleted by treating cells with sodium azide and 2-deoxyglucose. Chromatin conformation was analysed in both live and permeabilised HeLa cells using FLIM-FRET, high resolution fluorescence microscopy and by electron spectroscopic imaging microscopy. We show that chromatin compaction following ATP depletion is not caused by loss of transcription activity and that it can occur at a similar level in both interphase and mitotic cells. Analysis of both live and permeabilised HeLa cells shows that chromatin conformation within nuclei is strongly influenced by the levels of divalent cations, including calcium and magnesium. While ATP depletion results in an increase in the level of unbound calcium, chromatin condensation still occurs even in the presence of a calcium chelator. Chromatin compaction is shown to be strongly affected by small changes in the levels of polyamines, including spermine and spermidine. The data are consistent with a model in which the increased intracellular pool of polyamines and divalent cations, resulting from depletion of ATP, bind to DNA and contribute to the large scale hyper-compaction of chromatin by a charge neutralisation mechanism.

  8. A role for chromatin topology in imprinted domain regulation.

    Science.gov (United States)

    MacDonald, William A; Sachani, Saqib S; White, Carlee R; Mann, Mellissa R W

    2016-02-01

    Recently, many advancements in genome-wide chromatin topology and nuclear architecture have unveiled the complex and hidden world of the nucleus, where chromatin is organized into discrete neighbourhoods with coordinated gene expression. This includes the active and inactive X chromosomes. Using X chromosome inactivation as a working model, we utilized publicly available datasets together with a literature review to gain insight into topologically associated domains, lamin-associated domains, nucleolar-associating domains, scaffold/matrix attachment regions, and nucleoporin-associated chromatin and their role in regulating monoallelic expression. Furthermore, we comprehensively review for the first time the role of chromatin topology and nuclear architecture in the regulation of genomic imprinting. We propose that chromatin topology and nuclear architecture are important regulatory mechanisms for directing gene expression within imprinted domains. Furthermore, we predict that dynamic changes in chromatin topology and nuclear architecture play roles in tissue-specific imprint domain regulation during early development and differentiation.

  9. Architecture

    OpenAIRE

    Clear, Nic

    2014-01-01

    When discussing science fiction’s relationship with architecture, the usual practice is to look at the architecture “in” science fiction—in particular, the architecture in SF films (see Kuhn 75-143) since the spaces of literary SF present obvious difficulties as they have to be imagined. In this essay, that relationship will be reversed: I will instead discuss science fiction “in” architecture, mapping out a number of architectural movements and projects that can be viewed explicitly as scien...

  10. Oligomer formation and G-quadruplex binding by purified murine Rif1 protein, a key organizer of higher-order chromatin architecture.

    Science.gov (United States)

    Moriyama, Kenji; Yoshizawa-Sugata, Naoko; Masai, Hisao

    2018-03-09

    Rap1-interacting protein 1 (Rif1) regulates telomere length in budding yeast. We previously reported that, in metazoans and fission yeast, Rif1 also plays pivotal roles in controlling genome-wide DNA replication timing. We proposed that Rif1 may assemble chromatin compartments that contain specific replication-timing domains by promoting chromatin loop formation. Rif1 also is involved in DNA lesion repair, restart after replication fork collapse, anti-apoptosis activities, replicative senescence, and transcriptional regulation. Although multiple physiological functions of Rif1 have been characterized, biochemical and structural information on mammalian Rif1 is limited, mainly because of difficulties in purifying the full-length protein. Here, we expressed and purified the 2418-amino-acid-long, full-length murine Rif1 as well as its partially truncated variants in human 293T cells. Hydrodynamic analyses indicated that Rif1 forms elongated or extended homo-oligomers in solution, consistent with the presence of a HEAT-type helical repeat segment known to adopt an elongated shape. We also observed that the purified murine Rif1 bound G-quadruplex (G4) DNA with high specificity and affinity, as was previously shown for Rif1 from fission yeast. Both the N-terminal (HEAT-repeat) and C-terminal segments were involved in oligomer formation and specifically bound G4 DNA, and the central intrinsically disordered polypeptide segment increased the affinity for G4. Of note, pulldown assays revealed that Rif1 simultaneously binds multiple G4 molecules. Our findings support a model in which Rif1 modulates chromatin loop structures through binding to multiple G4 assemblies and by holding chromatin fibers together. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. A transient ischemic environment induces reversible compaction of chromatin.

    Science.gov (United States)

    Kirmes, Ina; Szczurek, Aleksander; Prakash, Kirti; Charapitsa, Iryna; Heiser, Christina; Musheev, Michael; Schock, Florian; Fornalczyk, Karolina; Ma, Dongyu; Birk, Udo; Cremer, Christoph; Reid, George

    2015-11-05

    Cells detect and adapt to hypoxic and nutritional stress through immediate transcriptional, translational and metabolic responses. The environmental effects of ischemia on chromatin nanostructure were investigated using single molecule localization microscopy of DNA binding dyes and of acetylated histones, by the sensitivity of chromatin to digestion with DNAseI, and by fluorescence recovery after photobleaching (FRAP) of core and linker histones. Short-term oxygen and nutrient deprivation of the cardiomyocyte cell line HL-1 induces a previously undescribed chromatin architecture, consisting of large, chromatin-sparse voids interspersed between DNA-dense hollow helicoid structures 40-700 nm in dimension. The chromatin compaction is reversible, and upon restitution of normoxia and nutrients, chromatin transiently adopts a more open structure than in untreated cells. The compacted state of chromatin reduces transcription, while the open chromatin structure induced upon recovery provokes a transitory increase in transcription. Digestion of chromatin with DNAseI confirms that oxygen and nutrient deprivation induces compaction of chromatin. Chromatin compaction is associated with depletion of ATP and redistribution of the polyamine pool into the nucleus. FRAP demonstrates that core histones are not displaced from compacted chromatin; however, the mobility of linker histone H1 is considerably reduced, to an extent that far exceeds the difference in histone H1 mobility between heterochromatin and euchromatin. These studies exemplify the dynamic capacity of chromatin architecture to physically respond to environmental conditions, directly link cellular energy status to chromatin compaction and provide insight into the effect ischemia has on the nuclear architecture of cells.

  12. Chromatin is wonderful stuff.

    NARCIS (Netherlands)

    van Driel, R.

    2007-01-01

    Chromatin molecules have properties that set them aside from all other biomacromolecules in the cell. (i) Chromosomes, which are single chromatin molecules, are the largest macromolecules in eukaryotic cells. (ii) Chromatin molecules carry the cell's genetic and epigenetic information and all

  13. A novel Toxoplasma gondii nuclear factor TgNF3 is a dynamic chromatin-associated component, modulator of nucleolar architecture and parasite virulence.

    Directory of Open Access Journals (Sweden)

    Alejandro Olguin-Lamas

    2011-03-01

    Full Text Available In Toxoplasma gondii, cis-acting elements present in promoter sequences of genes that are stage-specifically regulated have been described. However, the nuclear factors that bind to these cis-acting elements and regulate promoter activities have not been identified. In the present study, we performed affinity purification, followed by proteomic analysis, to identify nuclear factors that bind to a stage-specific promoter in T. gondii. This led to the identification of several nuclear factors in T. gondii including a novel factor, designated herein as TgNF3. The N-terminal domain of TgNF3 shares similarities with the N-terminus of yeast nuclear FK506-binding protein (FKBP, known as a histone chaperone regulating gene silencing. Using anti-TgNF3 antibodies, HA-FLAG and YFP-tagged TgNF3, we show that TgNF3 is predominantly a parasite nucleolar, chromatin-associated protein that binds specifically to T. gondii gene promoters in vivo. Genome-wide analysis using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identified promoter occupancies by TgNF3. In addition, TgNF3 has a direct role in transcriptional control of genes involved in parasite metabolism, transcription and translation. The ectopic expression of TgNF3 in the tachyzoites revealed dynamic changes in the size of the nucleolus, leading to a severe attenuation of virulence in vivo. We demonstrate that TgNF3 physically interacts with H3, H4 and H2A/H2B assembled into bona fide core and nucleosome-associated histones. Furthermore, TgNF3 interacts specifically to histones in the context of stage-specific gene silencing of a promoter that lacks active epigenetic acetylated histone marks. In contrast to virulent tachyzoites, which express the majority of TgNF3 in the nucleolus, the protein is exclusively located in the cytoplasm of the avirulent bradyzoites. We propose a model where TgNF3 acts essentially to coordinate nucleolus and nuclear functions by modulating

  14. Chromatin Structure and Function

    CERN Document Server

    Wolffe, Alan P

    1999-01-01

    The Third Edition of Chromatin: Structure and Function brings the reader up-to-date with the remarkable progress in chromatin research over the past three years. It has been extensively rewritten to cover new material on chromatin remodeling, histone modification, nuclear compartmentalization, DNA methylation, and transcriptional co-activators and co-repressors. The book is written in a clear and concise fashion, with 60 new illustrations. Chromatin: Structure and Function provides the reader with a concise and coherent account of the nature, structure, and assembly of chromatin and its active

  15. The Chromatin Scaffold Protein SAFB1 Renders Chromatin Permissive for DNA Damage Signaling

    DEFF Research Database (Denmark)

    Altmeyer, Matthias; Toledo Lazaro, Luis Ignacio; Gudjonsson, Thorkell

    2013-01-01

    Although the general relevance of chromatin modifications for genotoxic stress signaling, cell-cycle checkpoint activation, and DNA repair is well established, how these modifications reach initial thresholds in order to trigger robust responses remains largely unexplored. Here, we identify...... the chromatin-associated scaffold attachment factor SAFB1 as a component of the DNA damage response and show that SAFB1 cooperates with histone acetylation to allow for efficient γH2AX spreading and genotoxic stress signaling. SAFB1 undergoes a highly dynamic exchange at damaged chromatin in a poly......(ADP-ribose)-polymerase 1- and poly(ADP-ribose)-dependent manner and is required for unperturbed cell-cycle checkpoint activation and guarding cells against replicative stress. Altogether, our data reveal that transient recruitment of an architectural chromatin component is required in order to overcome physiological...

  16. Heterogeneous chromatin target model

    International Nuclear Information System (INIS)

    Watanabe, Makoto

    1996-01-01

    The higher order structure of the entangled chromatin fibers in a chromosome plays a key role in molecular control mechanism involved in chromosome mutation due to ionizing radiations or chemical mutagens. The condensed superstructure of chromatin is not so rigid and regular as has been postulated in general. We have proposed a rheological explanation for the flexible network system ('chromatin network') that consists of the fluctuating assembly of nucleosome clusters linked with supertwisting DNA in a chromatin fiber ('Supertwisting Particulate Model'). We have proposed a 'Heterosensitive Target Model' for cellular radiosensitivity that is a modification of 'Heterogeneous Target Model'. The heterogeneity of chromatin target is derived from the highly condensed organization of chromatin segments consist of unstable and fragile sites in the fluctuating assembly of nucleosome clusters, namely 'supranucleosomal particles' or 'superbeads'. The models have been principally supported by our electron microscopic experiments employing 'surface - spreading whole - mount technique' since 1967. However, some deformation and artifacts in the chromatin structure are inevitable with these electron microscopic procedures. On the contrary, the 'atomic force microscope (AFM)' can be operated in liquid as well as in the air. A living specimen can be examined without any preparative procedures. Micromanipulation of the isolated chromosome is also possible by the precise positional control of a cantilever on the nanometer scale. The living human chromosomes were submerged in a solution of culture medium and observed by AFM using a liquid immersion cell. The surface - spreading whole - mount technique was applicable for this observation. The particulate chromatin segments of nucleosome clusters were clearly observed within mitotic human chromosomes in a living hydrated condition. These findings support the heterogeneity of chromatin target in a living cell. (J.P.N.)

  17. Chromatin replication and epigenome maintenance

    DEFF Research Database (Denmark)

    Alabert, Constance; Groth, Anja

    2012-01-01

    Stability and function of eukaryotic genomes are closely linked to chromatin structure and organization. During cell division the entire genome must be accurately replicated and the chromatin landscape reproduced on new DNA. Chromatin and nuclear structure influence where and when DNA replication...... initiates, whereas the replication process itself disrupts chromatin and challenges established patterns of genome regulation. Specialized replication-coupled mechanisms assemble new DNA into chromatin, but epigenome maintenance is a continuous process taking place throughout the cell cycle. If DNA...

  18. Reprogramming the chromatin landscape

    DEFF Research Database (Denmark)

    Miranda, Tina B; Voss, Ty C; Sung, Myong-Hee

    2013-01-01

    , mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER...... and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors...

  19. Identification of potential nuclear reprogramming and differentiation factors by a novel selection method for cloning chromatin-binding proteins

    International Nuclear Information System (INIS)

    Wang Liu; Zheng Aihua; Yi Ling; Xu Chongren; Ding Mingxiao; Deng Hongkui

    2004-01-01

    Nuclear reprogramming is critical for animal cloning and stem cell creation through nuclear transfer, which requires extensive remodeling of chromosomal architecture involving dramatic changes in chromatin-binding proteins. To understand the mechanism of nuclear reprogramming, it is critical to identify chromatin-binding factors specify the reprogramming process. In this report, we have developed a high-throughput selection method, based on T7 phage display and chromatin immunoprecipitation, to isolate chromatin-binding factors expressed in mouse embryonic stem cells using primary mouse embryonic fibroblast chromatin. Seven chromatin-binding proteins have been isolated by this method. We have also isolated several chromatin-binding proteins involved in hepatocyte differentiation. Our method provides a powerful tool to rapidly and selectively identify chromatin-binding proteins. The method can be used to study epigenetic modification of chromatin during nuclear reprogramming, cell differentiation, and transdifferentiation

  20. EBV Latency Types Adopt Alternative Chromatin Conformations

    Science.gov (United States)

    Tempera, Italo; Klichinsky, Michael; Lieberman, Paul M.

    2011-01-01

    Epstein-Barr Virus (EBV) can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C) assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp) or type III (Cp) gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer. PMID:21829357

  1. EBV latency types adopt alternative chromatin conformations.

    Directory of Open Access Journals (Sweden)

    Italo Tempera

    2011-07-01

    Full Text Available Epstein-Barr Virus (EBV can establish latent infections with distinct gene expression patterns referred to as latency types. These different latency types are epigenetically stable and correspond to different promoter utilization. Here we explore the three-dimensional conformations of the EBV genome in different latency types. We employed Chromosome Conformation Capture (3C assay to investigate chromatin loop formation between the OriP enhancer and the promoters that determine type I (Qp or type III (Cp gene expression. We show that OriP is in close physical proximity to Qp in type I latency, and to Cp in type III latency. The cellular chromatin insulator and boundary factor CTCF was implicated in EBV chromatin loop formation. Combining 3C and ChIP assays we found that CTCF is physically associated with OriP-Qp loop formation in type I and OriP-Cp loop formation in type III latency. Mutations in the CTCF binding site located at Qp disrupt loop formation between Qp and OriP, and lead to the activation of Cp transcription. Mutation of the CTCF binding site at Cp, as well as siRNA depletion of CTCF eliminates both OriP-associated loops, indicating that CTCF plays an integral role in loop formation. These data indicate that epigenetically stable EBV latency types adopt distinct chromatin architectures that depend on CTCF and mediate alternative promoter targeting by the OriP enhancer.

  2. Capturing Structural Heterogeneity in Chromatin Fibers.

    Science.gov (United States)

    Ekundayo, Babatunde; Richmond, Timothy J; Schalch, Thomas

    2017-10-13

    Chromatin fiber organization is implicated in processes such as transcription, DNA repair and chromosome segregation, but how nucleosomes interact to form higher-order structure remains poorly understood. We solved two crystal structures of tetranucleosomes with approximately 11-bp DNA linker length at 5.8 and 6.7 Å resolution. Minimal intramolecular nucleosome-nucleosome interactions result in a fiber model resembling a flat ribbon that is compatible with a two-start helical architecture, and that exposes histone and DNA surfaces to the environment. The differences in the two structures combined with electron microscopy reveal heterogeneous structural states, and we used site-specific chemical crosslinking to assess the diversity of nucleosome-nucleosome interactions through identification of structure-sensitive crosslink sites that provide a means to characterize fibers in solution. The chromatin fiber architectures observed here provide a basis for understanding heterogeneous chromatin higher-order structures as they occur in a genomic context. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Proteomic interrogation of human chromatin.

    Directory of Open Access Journals (Sweden)

    Mariana P Torrente

    Full Text Available Chromatin proteins provide a scaffold for DNA packaging and a basis for epigenetic regulation and genomic maintenance. Despite understanding its functional roles, mapping the chromatin proteome (i.e. the "Chromatome" is still a continuing process. Here, we assess the biological specificity and proteomic extent of three distinct chromatin preparations by identifying proteins in selected chromatin-enriched fractions using mass spectrometry-based proteomics. These experiments allowed us to produce a chromatin catalog, including several proteins ranging from highly abundant histone proteins to less abundant members of different chromatin machinery complexes. Using a Normalized Spectral Abundance Factor approach, we quantified relative abundances of the proteins across the chromatin enriched fractions giving a glimpse into their chromosomal abundance. The large-scale data sets also allowed for the discovery of a variety of novel post-translational modifications on the identified chromatin proteins. With these comparisons, we find one of the probed methods to be qualitatively superior in specificity for chromatin proteins, but inferior in proteomic extent, evidencing a compromise that must be made between biological specificity and broadness of characterization. Additionally, we attempt to identify proteins in eu- and heterochromatin, verifying the enrichments by characterizing the post-translational modifications detected on histone proteins from these chromatin regions. In summary, our results provide insights into the value of different methods to extract chromatin-associated proteins and provide starting points to study the factors that may be involved in directing gene expression and other chromatin-related processes.

  4. Effects of fast neutrons on chromatin: dependence on chromatin structure

    Energy Technology Data Exchange (ETDEWEB)

    Radu, L. [Dept. of Molecular Genetics, V. Babes National Inst., Bd. Timisoara, Bucharest (Romania); Constantinescu, B. [Dept. of Cyclotron, H. Hulubei National Inst., Bucharest (Romania); Gazdaru, D. [Dept. of Biophysics, Physics Faculty, Univ. of Bucharest (Romania)

    2002-07-01

    The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin-proflavine complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl chloride and acridine orange coupled to chromatin. For both normal and tumor chromatin, the intensity of intrinsic fluorescence specific for acidic and basic proteins decreased with increasing dose. The relative contributions of the excited-state lifetime of proflavine bound to chromatin were reduced upon fast-neutron irradiation, indicating a decrease in the proportion of chromatin DNA available for ligand binding. The Forster energy transfer efficiencies were also modified by irradiation. These effects were larger for chromatin from tumor tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and acidic and basic proteins, as well as in global chromatin structure. The radiosensitivity of chromatin extracted from tumor tissue seems to be higher than that of chromatin extracted from normal tissue, probably because of its higher euchromatin (loose)-heterochromatin (compact) ratio. (author)

  5. Effects of fast neutrons on chromatin: dependence on chromatin structure

    International Nuclear Information System (INIS)

    Radu, L.; Constantinescu, B.; Gazdaru, D.

    2002-01-01

    The effects of fast neutrons (10-100 Gy) on chromatin extracted from normal (liver of Wistar rats) and tumor (Walker carcinosarcoma maintained on Wistar rats) tissues were compared. The spectroscopic assays used were (i) chromatin intrinsic fluorescence, (ii) time-resolved fluorescence of chromatin-proflavine complexes, and (iii) fluorescence resonance energy transfer (FRET) between dansyl chloride and acridine orange coupled to chromatin. For both normal and tumor chromatin, the intensity of intrinsic fluorescence specific for acidic and basic proteins decreased with increasing dose. The relative contributions of the excited-state lifetime of proflavine bound to chromatin were reduced upon fast-neutron irradiation, indicating a decrease in the proportion of chromatin DNA available for ligand binding. The Forster energy transfer efficiencies were also modified by irradiation. These effects were larger for chromatin from tumor tissue. In the range 0-100 Gy, fast neutrons induced alterations in DNA and acidic and basic proteins, as well as in global chromatin structure. The radiosensitivity of chromatin extracted from tumor tissue seems to be higher than that of chromatin extracted from normal tissue, probably because of its higher euchromatin (loose)-heterochromatin (compact) ratio. (author)

  6. Higher order chromatin organization in cancer

    Science.gov (United States)

    Reddy, Karen L.; Feinberg, Andrew P.

    2013-01-01

    In spite of our increased understanding of how genomes are dysregulated in cancer and a plethora of molecular diagnostic tools, the front line and ‘gold standard’ detection of cancer remains the pathologist’s detection of gross changes in cellular and tissue structure, most strikingly nuclear dis-organization. In fact, for over 140 years it has been noted that nuclear morphology is often disrupted in cancer. Even today, nuclear morphology measures include nuclear size, shape, DNA content (ploidy) and ‘chromatin organization’. Given the importance of nuclear shape to diagnoses of cancer phenotypes, it is surprising and frustrating that we currently lack a detailed understanding to explain these changes and how they might arise and relate to molecular events in the cell. It is an implicit hypothesis that perturbation of chromatin and epigenetic signatures may lead to alterations in nuclear structure (or vice versa) and that these perturbations lie at the heart of cancer genesis. In this review, we attempt to synthesize research leading to our current understanding on how chromatin interactions at the nuclear lamina, epigenetic modulation and gene regulation may intersect in cancer and offer a perspective on critical experiments that would help clarify how nuclear architecture may contribute to the cancerous phenotype. We also discuss the historical understanding of nuclear structure in normal cells and as a diagnostic in cancer. PMID:23266653

  7. Chromatin replication and histone dynamics

    DEFF Research Database (Denmark)

    Alabert, Constance; Jasencakova, Zuzana; Groth, Anja

    2017-01-01

    Inheritance of the DNA sequence and its proper organization into chromatin is fundamental for genome stability and function. Therefore, how specific chromatin structures are restored on newly synthesized DNA and transmitted through cell division remains a central question to understand cell fate...... choices and self-renewal. Propagation of genetic information and chromatin-based information in cycling cells entails genome-wide disruption and restoration of chromatin, coupled with faithful replication of DNA. In this chapter, we describe how cells duplicate the genome while maintaining its proper...... organization into chromatin. We reveal how specialized replication-coupled mechanisms rapidly assemble newly synthesized DNA into nucleosomes, while the complete restoration of chromatin organization including histone marks is a continuous process taking place throughout the cell cycle. Because failure...

  8. Chromatin dynamics in genome stability

    DEFF Research Database (Denmark)

    Nair, Nidhi; Shoaib, Muhammad; Sørensen, Claus Storgaard

    2017-01-01

    Genomic DNA is compacted into chromatin through packaging with histone and non-histone proteins. Importantly, DNA accessibility is dynamically regulated to ensure genome stability. This is exemplified in the response to DNA damage where chromatin relaxation near genomic lesions serves to promote...... access of relevant enzymes to specific DNA regions for signaling and repair. Furthermore, recent data highlight genome maintenance roles of chromatin through the regulation of endogenous DNA-templated processes including transcription and replication. Here, we review research that shows the importance...... of chromatin structure regulation in maintaining genome integrity by multiple mechanisms including facilitating DNA repair and directly suppressing endogenous DNA damage....

  9. Contribution of Topological Domains and Loop Formation to 3D Chromatin Organization

    Directory of Open Access Journals (Sweden)

    Vuthy Ea

    2015-07-01

    Full Text Available Recent investigations on 3D chromatin folding revealed that the eukaryote genomes are both highly compartmentalized and extremely dynamic. This review presents the most recent advances in topological domains’ organization of the eukaryote genomes and discusses the relationship to chromatin loop formation. CTCF protein appears as a central factor of these two organization levels having either a strong insulating role at TAD borders, or a weaker architectural role in chromatin loop formation. TAD borders directly impact on chromatin dynamics by restricting contacts within specific genomic portions thus confining chromatin loop formation within TADs. We discuss how sub-TAD chromatin dynamics, constrained into a recently described statistical helix conformation, can produce functional interactions by contact stabilization.

  10. Chromatin Flavors: Chromatin composition and domain organization in Drosophila melanogaster

    NARCIS (Netherlands)

    J.G. van Bemmel (Joke)

    2012-01-01

    textabstractChromatin was originally identified by W. Flemming in 1882 as not much more than the stainable substance of the cell nucleus. Flemming named this substance according to the Greek word “chroma”, meaning color. In 1911 chromatin was characterized as proteins, named histones, that

  11. Optical tweezers stretching of chromatin

    NARCIS (Netherlands)

    Pope, L.H.; Bennink, Martin L.; Greve, Jan

    2003-01-01

    Recently significant success has emerged from exciting research involving chromatin stretching using optical tweezers. These experiments, in which a single chromatin fibre is attached by one end to a micron-sized bead held in an optical trap and to a solid surface or second bead via the other end,

  12. The condensed chromatin fiber: an allosteric chemo-mechanical machine for signal transduction and genome processing

    International Nuclear Information System (INIS)

    Lesne, Annick; Victor, Jean–Marc; Bécavin, Christophe

    2012-01-01

    Allostery is a key concept of molecular biology which refers to the control of an enzyme activity by an effector molecule binding the enzyme at another site rather than the active site (allos = other in Greek). We revisit here allostery in the context of chromatin and argue that allosteric principles underlie and explain the functional architecture required for spacetime coordination of gene expression at all scales from DNA to the whole chromosome. We further suggest that this functional architecture is provided by the chromatin fiber itself. The structural, mechanical and topological features of the chromatin fiber endow chromosomes with a tunable signal transduction from specific (or nonspecific) effectors to specific (or nonspecific) active sites. Mechanical constraints can travel along the fiber all the better since the fiber is more compact and regular, which speaks in favor of the actual existence of the (so-called 30 nm) chromatin fiber. Chromatin fiber allostery reconciles both the physical and biochemical approaches of chromatin. We illustrate this view with two supporting specific examples. Moreover, from a methodological point of view, we suggest that the notion of chromatin fiber allostery is particularly relevant for systemic approaches. Finally we discuss the evolutionary power of allostery in the context of chromatin and its relation to modularity. (perspective)

  13. The condensed chromatin fiber: an allosteric chemo-mechanical machine for signal transduction and genome processing

    Science.gov (United States)

    Lesne, Annick; Bécavin, Christophe; Victor, Jean–Marc

    2012-02-01

    Allostery is a key concept of molecular biology which refers to the control of an enzyme activity by an effector molecule binding the enzyme at another site rather than the active site (allos = other in Greek). We revisit here allostery in the context of chromatin and argue that allosteric principles underlie and explain the functional architecture required for spacetime coordination of gene expression at all scales from DNA to the whole chromosome. We further suggest that this functional architecture is provided by the chromatin fiber itself. The structural, mechanical and topological features of the chromatin fiber endow chromosomes with a tunable signal transduction from specific (or nonspecific) effectors to specific (or nonspecific) active sites. Mechanical constraints can travel along the fiber all the better since the fiber is more compact and regular, which speaks in favor of the actual existence of the (so-called 30 nm) chromatin fiber. Chromatin fiber allostery reconciles both the physical and biochemical approaches of chromatin. We illustrate this view with two supporting specific examples. Moreover, from a methodological point of view, we suggest that the notion of chromatin fiber allostery is particularly relevant for systemic approaches. Finally we discuss the evolutionary power of allostery in the context of chromatin and its relation to modularity.

  14. Radiation response and chromatin dynamics

    International Nuclear Information System (INIS)

    Ikura, Tsuyoshi

    2009-01-01

    Described is a recent progress in studies of chromatin structural alterations induced by DNA damage by radiation. DNA in eukaryotes exists in the chromatin structure and different mechanisms of response to damage and repair of DNA from those in prokaryotes have been recognized. Chromatin is composed from its unit structure of mono-nucleosome, which is formed from DNA and an octamer of core histones of H2A, H2B, H3 and H4. When DNA is damaged, histone structural alterations are required for repair factors and checkpoint proteins to access the damaged site. At the actual genome damage, chemical modification of histone to work as a code occurs dependently on the damage where chromatin remodeling factors and histone chaperone participate for structural alteration and remodeling. As well, the exchange of histone variants and fluidization of histones are recently reported. Known chemical modification involves phosphorylation, acetylation and ubiquitination of H2AX (a variant of H2A), and acetylation and methylation of H3. Each complex of TIP60, NuA4 and INO80 is known to be included in the regulation of chromatin with damaged/repaired DNA for remodeling, but little is known about recruitment of the factors concerned at the damage site. Regulatory mechanisms in above chromatin dynamics with consideration of quality and timing of radiation should be further elucidated for understanding the precise response to DNA damage. (K.T.)

  15. Chromatin remodeling, development and disease

    International Nuclear Information System (INIS)

    Ko, Myunggon; Sohn, Dong H.; Chung, Heekyoung; Seong, Rho H.

    2008-01-01

    Development is a stepwise process in which multi-potent progenitor cells undergo lineage commitment, differentiation, proliferation and maturation to produce mature cells with restricted developmental potentials. This process is directed by spatiotemporally distinct gene expression programs that allow cells to stringently orchestrate intricate transcriptional activation or silencing events. In eukaryotes, chromatin structure contributes to developmental progression as a blueprint for coordinated gene expression by actively participating in the regulation of gene expression. Changes in higher order chromatin structure or covalent modification of its components are considered to be critical events in dictating lineage-specific gene expression during development. Mammalian cells utilize multi-subunit nuclear complexes to alter chromatin structure. Histone-modifying complex catalyzes covalent modifications of histone tails including acetylation, methylation, phosphorylation and ubiquitination. ATP-dependent chromatin remodeling complex, which disrupts histone-DNA contacts and induces nucleosome mobilization, requires energy from ATP hydrolysis for its catalytic activity. Here, we discuss the diverse functions of ATP-dependent chromatin remodeling complexes during mammalian development. In particular, the roles of these complexes during embryonic and hematopoietic development are reviewed in depth. In addition, pathological conditions such as tumor development that are induced by mutation of several key subunits of the chromatin remodeling complex are discussed, together with possible mechanisms that underlie tumor suppression by the complex

  16. Hierarchical role for transcription factors and chromatin structure in genome organization along adipogenesis

    DEFF Research Database (Denmark)

    Sarusi Portuguez, Avital; Schwartz, Michal; Siersbaek, Rasmus

    2017-01-01

    The three dimensional folding of mammalian genomes is cell type specific and difficult to alter suggesting that it is an important component of gene regulation. However, given the multitude of chromatin-associating factors, the mechanisms driving the colocalization of active chromosomal domains...... by PPARγ and Lpin1, undergoes orchestrated reorganization during adipogenesis. Coupling the dynamics of genome architecture with multiple chromatin datasets indicated that among all the transcription factors (TFs) tested, RXR is central to genome reorganization at the beginning of adipogenesis...

  17. Chromatin Remodeling and Plant Immunity.

    Science.gov (United States)

    Chen, W; Zhu, Q; Liu, Y; Zhang, Q

    Chromatin remodeling, an important facet of the regulation of gene expression in eukaryotes, is performed by two major types of multisubunit complexes, covalent histone- or DNA-modifying complexes, and ATP-dependent chromosome remodeling complexes. Snf2 family DNA-dependent ATPases constitute the catalytic subunits of ATP-dependent chromosome remodeling complexes, which accounts for energy supply during chromatin remodeling. Increasing evidence indicates a critical role of chromatin remodeling in the establishment of long-lasting, even transgenerational immune memory in plants, which is supported by the findings that DNA methylation, histone deacetylation, and histone methylation can prime the promoters of immune-related genes required for disease defense. So what are the links between Snf2-mediated ATP-dependent chromosome remodeling and plant immunity, and what mechanisms might support its involvement in disease resistance? © 2017 Elsevier Inc. All rights reserved.

  18. Chromatin challenges during DNA replication and repair

    DEFF Research Database (Denmark)

    Groth, Anja; Rocha, Walter; Verreault, Alain

    2007-01-01

    Inheritance and maintenance of the DNA sequence and its organization into chromatin are central for eukaryotic life. To orchestrate DNA-replication and -repair processes in the context of chromatin is a challenge, both in terms of accessibility and maintenance of chromatin organization. To meet...... the challenge of maintenance, cells have evolved efficient nucleosome-assembly pathways and chromatin-maturation mechanisms that reproduce chromatin organization in the wake of DNA replication and repair. The aim of this Review is to describe how these pathways operate and to highlight how the epigenetic...... landscape may be stably maintained even in the face of dramatic changes in chromatin structure....

  19. A Long-Distance Chromatin Affair

    NARCIS (Netherlands)

    Denker, Annette; de Laat, Wouter

    2015-01-01

    Changes in transcription factor binding sequences result in correlated changes in chromatin composition locally and at sites hundreds of kilobases away. New studies demonstrate that this concordance is mediated via spatial chromatin interactions that constitute regulatory modules of the human

  20. Guarding against Collateral Damage during Chromatin Transactions

    DEFF Research Database (Denmark)

    Altmeyer, Matthias; Lukas, Jiri

    2013-01-01

    Signal amplifications are vital for chromatin function, yet they also bear the risk of transforming into unrestrained, self-escalating, and potentially harmful responses. Examples of inbuilt limitations are emerging, revealing how chromatin transactions are confined within physiological boundaries....

  1. Chromatin Structure and Replication Origins: Determinants Of Chromosome Replication And Nuclear Organization

    Science.gov (United States)

    Smith, Owen K.; Aladjem, Mirit I.

    2014-01-01

    The DNA replication program is, in part, determined by the epigenetic landscape that governs local chromosome architecture and directs chromosome duplication. Replication must coordinate with other biochemical processes occurring concomitantly on chromatin, such as transcription and remodeling, to insure accurate duplication of both genetic and epigenetic features and to preserve genomic stability. The importance of genome architecture and chromatin looping in coordinating cellular processes on chromatin is illustrated by two recent sets of discoveries. First, chromatin-associated proteins that are not part of the core replication machinery were shown to affect the timing of DNA replication. These chromatin-associated proteins could be working in concert, or perhaps in competition, with the transcriptional machinery and with chromatin modifiers to determine the spatial and temporal organization of replication initiation events. Second, epigenetic interactions are mediated by DNA sequences that determine chromosomal replication. In this review we summarize recent findings and current models linking spatial and temporal regulation of the replication program with epigenetic signaling. We discuss these issues in the context of the genome’s three-dimensional structure with an emphasis on events occurring during the initiation of DNA replication. PMID:24905010

  2. Models of chromatin spatial organisation in the cell nucleus

    Science.gov (United States)

    Nicodemi, Mario

    2014-03-01

    In the cell nucleus chromosomes have a complex architecture serving vital functional purposes. Recent experiments have started unveiling the interaction map of DNA sites genome-wide, revealing different levels of organisation at different scales. The principles, though, which orchestrate such a complex 3D structure remain still mysterious. I will overview the scenario emerging from some classical polymer physics models of the general aspect of chromatin spatial organisation. The available experimental data, which can be rationalised in a single framework, support a picture where chromatin is a complex mixture of differently folded regions, self-organised across spatial scales according to basic physical mechanisms. I will also discuss applications to specific DNA loci, e.g. the HoxB locus, where models informed with biological details, and tested against targeted experiments, can help identifying the determinants of folding.

  3. Real-Time Tracking of Parental Histones Reveals Their Contribution to Chromatin Integrity Following DNA Damage.

    Science.gov (United States)

    Adam, Salomé; Dabin, Juliette; Chevallier, Odile; Leroy, Olivier; Baldeyron, Céline; Corpet, Armelle; Lomonte, Patrick; Renaud, Olivier; Almouzni, Geneviève; Polo, Sophie E

    2016-10-06

    Chromatin integrity is critical for cell function and identity but is challenged by DNA damage. To understand how chromatin architecture and the information that it conveys are preserved or altered following genotoxic stress, we established a system for real-time tracking of parental histones, which characterize the pre-damage chromatin state. Focusing on histone H3 dynamics after local UVC irradiation in human cells, we demonstrate that parental histones rapidly redistribute around damaged regions by a dual mechanism combining chromatin opening and histone mobilization on chromatin. Importantly, parental histones almost entirely recover and mix with new histones in repairing chromatin. Our data further define a close coordination of parental histone dynamics with DNA repair progression through the damage sensor DDB2 (DNA damage-binding protein 2). We speculate that this mechanism may contribute to maintaining a memory of the original chromatin landscape and may help preserve epigenome stability in response to DNA damage. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  4. Chromatin in embryonic stem cell neuronal differentiation.

    Science.gov (United States)

    Meshorer, E

    2007-03-01

    Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

  5. Systems Biological Determination of the Epi-Genomic Structure Function Relation: : Nucleosomal Association Changes, Intra/Inter Chromosomal Architecture, Transcriptional Structure Relationship, Simulations of Nucleosomal/Chromatin Fiber/Chromosome Architecture and Dynamics, System Biological/Medical Result Integration via the GLOBE 3D Genome Platform.

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); P.R. Cook (Peter); K. Rippe (Karsten); Gernot Längst; G. Wedemann (Gero); F.G. Grosveld (Frank)

    2010-01-01

    textabstractDespite our knowledge of the sequence of the human genome, the relation of its three-dimensional dynamic architecture with its function – the storage and expression of genetic information – remains one of the central unresolved issues of our age. It became very clear meanwhile that this

  6. UV-induced structural changes in chromatin

    International Nuclear Information System (INIS)

    Lang, H.; Zimmer, C.; Vengerov, Yu.Yu.

    1985-01-01

    UV-induced structural alterations of chromatin were studied by means of CD, electron microscopic, and gel electrophoretic measurements. The results indicate that chromatin undergoes serious structural changes after irradiation even at very low fluences. In the low fluence range the structural transitions from the higher ordered chromatin structure to the unfolded state occur without detectable changes in the content of histone H1 and of the core histones. Histone H1 disappears only at fluences above 10 kJ/m 2 . Furthermore, DNA in chromatin is much more sensitive against UV-irradiation and shows a higher degree of strand scission relative to free DNA. While fragmentation in free DNA occurs at fluences above 15 kJ/m 2 , it occurs even at 5.5 kJ/m 2 in the case of chromatin. The biological meaning of the observed UV-induced structural alterations of chromatin is discussed. (author)

  7. Chromatin dynamics during DSB repair

    Czech Academy of Sciences Publication Activity Database

    Falk, Martin; Lukášová, Emilie; Gabrielová, Barbora; Ondřej, Vladan; Kozubek, Stanislav

    2007-01-01

    Roč. 1773, č. 10 (2007), s. 1534-1545 ISSN 0167-4889 R&D Projects: GA ČR(CZ) GP204/06/P349; GA ČR(CZ) 1QS500040508; GA AV ČR(CZ) IAA1065203; GA MŠk(CZ) 1P05OC084 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chromatin structure * double- strand breaks (DSB) * DNA repair Subject RIV: BO - Biophysics Impact factor: 4.374, year: 2007

  8. Transcriptional networks and chromatin remodeling controlling adipogenesis

    DEFF Research Database (Denmark)

    Siersbæk, Rasmus; Nielsen, Ronni; Mandrup, Susanne

    2012-01-01

    Adipocyte differentiation is tightly controlled by a transcriptional cascade, which directs the extensive reprogramming of gene expression required to convert fibroblast-like precursor cells into mature lipid-laden adipocytes. Recent global analyses of transcription factor binding and chromatin...... remodeling have revealed 'snapshots' of this cascade and the chromatin landscape at specific time-points of differentiation. These studies demonstrate that multiple adipogenic transcription factors co-occupy hotspots characterized by an open chromatin structure and specific epigenetic modifications....... Such transcription factor hotspots are likely to represent key signaling nodes which integrate multiple adipogenic signals at specific chromatin sites, thereby facilitating coordinated action on gene expression....

  9. Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes

    Directory of Open Access Journals (Sweden)

    Dasgupta Dipayan

    2005-05-01

    Full Text Available Abstract Background Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group. Results In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes. Conclusion The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.

  10. Mediator and Cohesin Connect Gene Expression and Chromatin Architecture

    Science.gov (United States)

    Kagey, Michael H.; Newman, Jamie J.; Bilodeau, Steve; Zhan, Ye; Orlando, David A.; van Berkum, Nynke L.; Ebmeier, Christopher C.; Goossens, Jesse; Rahl, Peter B.; Levine, Stuart S.; Taatjes, Dylan J.; Dekker, Job; Young, Richard A.

    2010-01-01

    Summary Transcription factors control cell specific gene expression programs through interactions with diverse coactivators and the transcription apparatus. Gene activation may involve DNA loop formation between enhancer-bound transcription factors and the transcription apparatus at the core promoter, but this process is not well understood. We report here that Mediator and Cohesin physically and functionally connect the enhancers and core promoters of active genes in embryonic stem cells. Mediator, a transcriptional coactivator, forms a complex with Cohesin, which can form rings that connect two DNA segments. The Cohesin loading factor Nipbl is associated with Mediator/Cohesin complexes, providing a means to load Cohesin at promoters. DNA looping is observed between the enhancers and promoters occupied by Mediator and Cohesin. Mediator and Cohesin occupy different promoters in different cells, thus generating cell-type specific DNA loops linked to the gene expression program of each cell. PMID:20720539

  11. The architects of crenarchaeal chromatin : A biophysical characterization of chromatin proteins from Sulfolobus solfataricus

    NARCIS (Netherlands)

    Driessen, Rosalie Paula Catharina

    2014-01-01

    Understanding of chromatin organization and compaction in Archaea is currently limited. The genome of several megabasepairs long is folded by a set of small chromatin proteins to fit into the micron-sized cell. A first step in understanding archaeal chromatin organization is to study the action of

  12. Dietary polyphenols and chromatin remodeling.

    Science.gov (United States)

    Russo, Gian Luigi; Vastolo, Viviana; Ciccarelli, Marco; Albano, Luigi; Macchia, Paolo Emidio; Ungaro, Paola

    2017-08-13

    Polyphenols are the most abundant phytochemicals in fruits, vegetables, and plant-derived beverages. Recent findings suggest that polyphenols display the ability to reverse adverse epigenetic regulation involved in pathological conditions, such as obesity, metabolic disorder, cardiovascular and neurodegenerative diseases, and various forms of cancer. Epigenetics, defined as heritable changes to the transcriptome, independent from those occurring in the genome, includes DNA methylation, histone modifications, and posttranscriptional gene regulation by noncoding RNAs. Sinergistically and cooperatively, these processes regulate gene expression by changing chromatin organization and DNA accessibility. Such induced epigenetic changes can be inherited during cell division, resulting in permanent maintenance of the acquired phenotype, but they may also occur throughout an individual life-course and may ultimately influence phenotypic outcomes (health and disease risk). In the last decade, a number of studies have shown that nutrients can affect metabolic traits by altering the structure of chromatin and directly regulate both transcription and translational processes. In this context, dietary polyphenol-targeted epigenetics becomes an attractive approach for disease prevention and intervention. Here, we will review how polyphenols, including flavonoids, curcuminoids, and stilbenes, modulate the establishment and maintenance of key epigenetic marks, thereby influencing gene expression and, hence, disease risk and health.

  13. Modern techniques for the analysis of chromatin and nuclear organization in C. elegans.

    Science.gov (United States)

    Askjaer, Peter; Ercan, Sevinç; Meister, Peter

    2014-04-02

    In recent years, Caenorhabditis elegans has emerged as a new model to investigate the relationships between nuclear architecture, cellular differentiation, and organismal development. On one hand, C. elegans with its fixed lineage and transparent body is a great model organism to observe gene functions in vivo in specific cell types using microscopy. On the other hand, two different techniques have been applied in nematodes to identify binding sites for chromatin-associated proteins genome-wide: chromatin immunoprecipitation (ChIP), and Dam-mediated identification (DamID). We summarize here all three techniques together as they are complementary. We also highlight strengths and differences of the individual approaches.

  14. CTCF and CohesinSA-1 Mark Active Promoters and Boundaries of Repressive Chromatin Domains in Primary Human Erythroid Cells.

    Directory of Open Access Journals (Sweden)

    Laurie A Steiner

    Full Text Available CTCF and cohesinSA-1 are regulatory proteins involved in a number of critical cellular processes including transcription, maintenance of chromatin domain architecture, and insulator function. To assess changes in the CTCF and cohesinSA-1 interactomes during erythropoiesis, chromatin immunoprecipitation coupled with high throughput sequencing and mRNA transcriptome analyses via RNA-seq were performed in primary human hematopoietic stem and progenitor cells (HSPC and primary human erythroid cells from single donors.Sites of CTCF and cohesinSA-1 co-occupancy were enriched in gene promoters in HSPC and erythroid cells compared to single CTCF or cohesin sites. Cell type-specific CTCF sites in erythroid cells were linked to highly expressed genes, with the opposite pattern observed in HSPCs. Chromatin domains were identified by ChIP-seq with antibodies against trimethylated lysine 27 histone H3, a modification associated with repressive chromatin. Repressive chromatin domains increased in both number and size during hematopoiesis, with many more repressive domains in erythroid cells than HSPCs. CTCF and cohesinSA-1 marked the boundaries of these repressive chromatin domains in a cell-type specific manner.These genome wide data, changes in sites of protein occupancy, chromatin architecture, and related gene expression, support the hypothesis that CTCF and cohesinSA-1 have multiple roles in the regulation of gene expression during erythropoiesis including transcriptional regulation at gene promoters and maintenance of chromatin architecture. These data from primary human erythroid cells provide a resource for studies of normal and perturbed erythropoiesis.

  15. Condensins Exert Force on Chromatin-Nuclear Envelope Tethers to Mediate Nucleoplasmic Reticulum Formation in Drosophila melanogaster

    Science.gov (United States)

    Bozler, Julianna; Nguyen, Huy Q.; Rogers, Gregory C.; Bosco, Giovanni

    2014-01-01

    Although the nuclear envelope is known primarily for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue-specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology. PMID:25552604

  16. Condensins exert force on chromatin-nuclear envelope tethers to mediate nucleoplasmic reticulum formation in Drosophila melanogaster.

    Science.gov (United States)

    Bozler, Julianna; Nguyen, Huy Q; Rogers, Gregory C; Bosco, Giovanni

    2014-12-30

    Although the nuclear envelope is known primarily for its role as a boundary between the nucleus and cytoplasm in eukaryotes, it plays a vital and dynamic role in many cellular processes. Studies of nuclear structure have revealed tissue-specific changes in nuclear envelope architecture, suggesting that its three-dimensional structure contributes to its functionality. Despite the importance of the nuclear envelope, the factors that regulate and maintain nuclear envelope shape remain largely unexplored. The nuclear envelope makes extensive and dynamic interactions with the underlying chromatin. Given this inexorable link between chromatin and the nuclear envelope, it is possible that local and global chromatin organization reciprocally impact nuclear envelope form and function. In this study, we use Drosophila salivary glands to show that the three-dimensional structure of the nuclear envelope can be altered with condensin II-mediated chromatin condensation. Both naturally occurring and engineered chromatin-envelope interactions are sufficient to allow chromatin compaction forces to drive distortions of the nuclear envelope. Weakening of the nuclear lamina further enhanced envelope remodeling, suggesting that envelope structure is capable of counterbalancing chromatin compaction forces. Our experiments reveal that the nucleoplasmic reticulum is born of the nuclear envelope and remains dynamic in that they can be reabsorbed into the nuclear envelope. We propose a model where inner nuclear envelope-chromatin tethers allow interphase chromosome movements to change nuclear envelope morphology. Therefore, interphase chromatin compaction may be a normal mechanism that reorganizes nuclear architecture, while under pathological conditions, such as laminopathies, compaction forces may contribute to defects in nuclear morphology. Copyright © 2015 Bozler et al.

  17. Chromatin-modifying proteins in cancer

    DEFF Research Database (Denmark)

    Fog, Cathrine K; Jensen, Klaus T; Lund, Anders Henrik

    2007-01-01

    -despite the fact that all cells in the organism contain the same genetic information. A large amount of data gathered over the last decades has demonstrated that deregulation of chromatin-modifying proteins is etiologically involved in the development and progression of cancer. Here we discuss how epigenetic...... alterations influence cancer development and review known cancer-associated alterations in chromatin-modifying proteins....

  18. A microscopic analysis of Arabidopsis chromatin

    NARCIS (Netherlands)

    Willemse, J.J.

    2007-01-01

    Genetic information of eukaryotic organisms is stored as DNA in the nuclei of their cells. Nuclear DNA is associated with several proteins, which together form chromatin. The most abundant chromatin proteins arehistones,they arrange the initial packaging step of the DNA. DNA

  19. Chromatin dynamics resolved with force spectroscopy

    NARCIS (Netherlands)

    Chien, Fan-Tso

    2011-01-01

    In eukaryotic cells, genomic DNA is organized in chromatin fibers composed of nucleosomes as structural units. A nucleosome contains 1.7 turns of DNA wrapped around a histone octamer and is connected to the adjacent nucleosomes with linker DNA. The folding of chromatin fibers effectively increases

  20. Transcription Through Chromatin - Dynamic Organization of Genes

    Indian Academy of Sciences (India)

    different proteins involved in the synthesis of mRNA from the. DNA template. ... CBP - CREB Binding Protein. CHRAC. Chromatin .... nucleosomal interactions, and thereby change the chromatin structure, as per the ..... methyltransferases in gene regulation is yet to be elucidated. .... Molecular Biology and. Genetics Unit.

  1. Chromatin Remodelers: From Function to Dysfunction

    Directory of Open Access Journals (Sweden)

    Gernot Längst

    2015-06-01

    Full Text Available Chromatin remodelers are key players in the regulation of chromatin accessibility and nucleosome positioning on the eukaryotic DNA, thereby essential for all DNA dependent biological processes. Thus, it is not surprising that upon of deregulation of those molecular machines healthy cells can turn into cancerous cells. Even though the remodeling enzymes are very abundant and a multitude of different enzymes and chromatin remodeling complexes exist in the cell, the particular remodeling complex with its specific nucleosome positioning features must be at the right place at the right time in order to ensure the proper regulation of the DNA dependent processes. To achieve this, chromatin remodeling complexes harbor protein domains that specifically read chromatin targeting signals, such as histone modifications, DNA sequence/structure, non-coding RNAs, histone variants or DNA bound interacting proteins. Recent studies reveal the interaction between non-coding RNAs and chromatin remodeling complexes showing importance of RNA in remodeling enzyme targeting, scaffolding and regulation. In this review, we summarize current understanding of chromatin remodeling enzyme targeting to chromatin and their role in cancer development.

  2. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure.

    Science.gov (United States)

    Rosa-Garrido, Manuel; Chapski, Douglas J; Schmitt, Anthony D; Kimball, Todd H; Karbassi, Elaheh; Monte, Emma; Balderas, Enrique; Pellegrini, Matteo; Shih, Tsai-Ting; Soehalim, Elizabeth; Liem, David; Ping, Peipei; Galjart, Niels J; Ren, Shuxun; Wang, Yibin; Ren, Bing; Vondriska, Thomas M

    2017-10-24

    Cardiovascular disease is associated with epigenomic changes in the heart; however, the endogenous structure of cardiac myocyte chromatin has never been determined. To investigate the mechanisms of epigenomic function in the heart, genome-wide chromatin conformation capture (Hi-C) and DNA sequencing were performed in adult cardiac myocytes following development of pressure overload-induced hypertrophy. Mice with cardiac-specific deletion of CTCF (a ubiquitous chromatin structural protein) were generated to explore the role of this protein in chromatin structure and cardiac phenotype. Transcriptome analyses by RNA-seq were conducted as a functional readout of the epigenomic structural changes. Depletion of CTCF was sufficient to induce heart failure in mice, and human patients with heart failure receiving mechanical unloading via left ventricular assist devices show increased CTCF abundance. Chromatin structural analyses revealed interactions within the cardiac myocyte genome at 5-kb resolution, enabling examination of intra- and interchromosomal events, and providing a resource for future cardiac epigenomic investigations. Pressure overload or CTCF depletion selectively altered boundary strength between topologically associating domains and A/B compartmentalization, measurements of genome accessibility. Heart failure involved decreased stability of chromatin interactions around disease-causing genes. In addition, pressure overload or CTCF depletion remodeled long-range interactions of cardiac enhancers, resulting in a significant decrease in local chromatin interactions around these functional elements. These findings provide a high-resolution chromatin architecture resource for cardiac epigenomic investigations and demonstrate that global structural remodeling of chromatin underpins heart failure. The newly identified principles of endogenous chromatin structure have key implications for epigenetic therapy. © 2017 The Authors.

  3. Architectural prototyping

    DEFF Research Database (Denmark)

    Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2004-01-01

    A major part of software architecture design is learning how specific architectural designs balance the concerns of stakeholders. We explore the notion of "architectural prototypes", correspondingly architectural prototyping, as a means of using executable prototypes to investigate stakeholders...

  4. Architecture on Architecture

    DEFF Research Database (Denmark)

    Olesen, Karen

    2016-01-01

    that is not scientific or academic but is more like a latent body of data that we find embedded in existing works of architecture. This information, it is argued, is not limited by the historical context of the work. It can be thought of as a virtual capacity – a reservoir of spatial configurations that can...... correlation between the study of existing architectures and the training of competences to design for present-day realities.......This paper will discuss the challenges faced by architectural education today. It takes as its starting point the double commitment of any school of architecture: on the one hand the task of preserving the particular knowledge that belongs to the discipline of architecture, and on the other hand...

  5. Structured illumination to spatially map chromatin motions.

    Science.gov (United States)

    Bonin, Keith; Smelser, Amanda; Moreno, Naike Salvador; Holzwarth, George; Wang, Kevin; Levy, Preston; Vidi, Pierre-Alexandre

    2018-05-01

    We describe a simple optical method that creates structured illumination of a photoactivatable probe and apply this method to characterize chromatin motions in nuclei of live cells. A laser beam coupled to a diffractive optical element at the back focal plane of an excitation objective generates an array of near diffraction-limited beamlets with FWHM of 340  ±  30  nm, which simultaneously photoactivate a 7  ×  7 matrix pattern of GFP-labeled histones, with spots 1.70  μm apart. From the movements of the photoactivated spots, we map chromatin diffusion coefficients at multiple microdomains of the cell nucleus. The results show correlated motions of nearest chromatin microdomain neighbors, whereas chromatin movements are uncorrelated at the global scale of the nucleus. The method also reveals a DNA damage-dependent decrease in chromatin diffusion. The diffractive optical element instrumentation can be easily and cheaply implemented on commercial inverted fluorescence microscopes to analyze adherent cell culture models. A protocol to measure chromatin motions in nonadherent human hematopoietic stem and progenitor cells is also described. We anticipate that the method will contribute to the identification of the mechanisms regulating chromatin mobility, which influences most genomic processes and may underlie the biogenesis of genomic translocations associated with hematologic malignancies. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  6. Effect of hyperthermia on replicating chromatin

    International Nuclear Information System (INIS)

    Warters, R.L.; Roti Roti, J.L.

    1981-01-01

    The extent of heat-induced structural alterations in chromatin containing nascent (pulse-labeled) DNA was assayed using the enzyme micrococcal nuclease. The basic nucleosome structure in nascent and mature chromatin of S-phase cells appeared unaltered for up to 16 hr after exposure to hyperthermic temperatures as high as 48 0 C for 15 min. However, the rate of nuclease digestion of DNA in both nascent and mature chromatin is inhibited following exposure to hyperthermic temperatures. In unheated cells, pulse-labeled nascent DNA matured into mature chromatin structure with a half-time of 2.5 min. The half-time for the maturation of pulse-labeled DNA from nascent into mature chromatin increased in a linear manner as a function of increasing temperature of exposure with constant heating time at temperatures above 43 0 C. Both the reduced nuclease digestibility of nascent DNA and the increased time for chromatin structural changes could be due to the increased protein mass of chromatin following hyperthermia

  7. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.

    2013-10-17

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  8. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.; Kyriazopoulou-Panagiotopoulou, S.; Grubert, F.; Zaugg, J. B.; Kundaje, A.; Liu, Y.; Boyle, A. P.; Zhang, Q. C.; Zakharia, F.; Spacek, D. V.; Li, J.; Xie, D.; Olarerin-George, A.; Steinmetz, L. M.; Hogenesch, J. B.; Kellis, M.; Batzoglou, S.; Snyder, M.

    2013-01-01

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  9. Put your 3D glasses on: plant chromatin is on show

    KAUST Repository

    Rodriguez Granados, Natalia Yaneth; Ramirez Prado, Juan Sebastian; Veluchamy, Alaguraj; Latrasse, David; Raynaud, Cé cile; Crespi, Martin; Ariel, Federico; Benhamed, Moussa

    2016-01-01

    The three-dimensional organization of the eukaryotic nucleus and its chromosomal conformation have emerged as important features in the complex network of mechanisms behind gene activity and genome connectivity dynamics, which can be evidenced in the regionalized chromosomal spatial distribution and the clustering of diverse genomic regions with similar expression patterns. The development of chromatin conformation capture (3C) techniques has permitted the elucidation of commonalities between the eukaryotic phyla, as well as important differences among them. The growing number of studies in the field performed in plants has shed light on the structural and regulatory features of these organisms. For instance, it has been proposed that plant chromatin can be arranged into different conformations such as Rabl, Rosette-like, and Bouquet, and that both short- and long-range chromatin interactions occur in Arabidopsis. In this review, we compile the current knowledge about chromosome architecture characteristics in plants, as well as the molecular events and elements (including long non-coding RNAs, histone and DNA modifications, chromatin remodeling complexes, and transcription factors) shaping the genome three-dimensional conformation. Furthermore, we discuss the developmental outputs of genome topology-mediated gene expression regulation. It is becoming increasingly clear that new tools and techniques with higher resolution need to be developed and implemented in Arabidopsis and other model plants in order to better understand chromosome architecture dynamics, from an integrative perspective with other fields of plant biology such as development, stress biology, and finally agriculture. © 2016 The Author 2016.

  10. Put your 3D glasses on: plant chromatin is on show

    KAUST Repository

    Rodriguez Granados, Natalia Yaneth

    2016-04-30

    The three-dimensional organization of the eukaryotic nucleus and its chromosomal conformation have emerged as important features in the complex network of mechanisms behind gene activity and genome connectivity dynamics, which can be evidenced in the regionalized chromosomal spatial distribution and the clustering of diverse genomic regions with similar expression patterns. The development of chromatin conformation capture (3C) techniques has permitted the elucidation of commonalities between the eukaryotic phyla, as well as important differences among them. The growing number of studies in the field performed in plants has shed light on the structural and regulatory features of these organisms. For instance, it has been proposed that plant chromatin can be arranged into different conformations such as Rabl, Rosette-like, and Bouquet, and that both short- and long-range chromatin interactions occur in Arabidopsis. In this review, we compile the current knowledge about chromosome architecture characteristics in plants, as well as the molecular events and elements (including long non-coding RNAs, histone and DNA modifications, chromatin remodeling complexes, and transcription factors) shaping the genome three-dimensional conformation. Furthermore, we discuss the developmental outputs of genome topology-mediated gene expression regulation. It is becoming increasingly clear that new tools and techniques with higher resolution need to be developed and implemented in Arabidopsis and other model plants in order to better understand chromosome architecture dynamics, from an integrative perspective with other fields of plant biology such as development, stress biology, and finally agriculture. © 2016 The Author 2016.

  11. SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae.

    Directory of Open Access Journals (Sweden)

    Mickaël Durand-Dubief

    2012-09-01

    Full Text Available Budding yeast centromeres are sequence-defined point centromeres and are, unlike in many other organisms, not embedded in heterochromatin. Here we show that Fun30, a poorly understood SWI/SNF-like chromatin remodeling factor conserved in humans, promotes point centromere function through the formation of correct chromatin architecture at centromeres. Our determination of the genome-wide binding and nucleosome positioning properties of Fun30 shows that this enzyme is consistently enriched over centromeres and that a majority of CENs show Fun30-dependent changes in flanking nucleosome position and/or CEN core micrococcal nuclease accessibility. Fun30 deletion leads to defects in histone variant Htz1 occupancy genome-wide, including at and around most centromeres. FUN30 genetically interacts with CSE4, coding for the centromere-specific variant of histone H3, and counteracts the detrimental effect of transcription through centromeres on chromosome segregation and suppresses transcriptional noise over centromere CEN3. Previous work has shown a requirement for fission yeast and mammalian homologs of Fun30 in heterochromatin assembly. As centromeres in budding yeast are not embedded in heterochromatin, our findings indicate a direct role of Fun30 in centromere chromatin by promoting correct chromatin architecture.

  12. Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

    KAUST Repository

    Bigeard, Jean; Rayapuram, Naganand; Pflieger, Delphine; Hirt, Heribert

    2014-01-01

    In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

  13. Phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins

    KAUST Repository

    Bigeard, Jean

    2014-07-10

    In eukaryotes, most of the DNA is located in the nucleus where it is organized with histone proteins in a higher order structure as chromatin. Chromatin and chromatin-associated proteins contribute to DNA-related processes such as replication and transcription as well as epigenetic regulation. Protein functions are often regulated by PTMs among which phosphorylation is one of the most abundant PTM. Phosphorylation of proteins affects important properties, such as enzyme activity, protein stability, or subcellular localization. We here describe the main specificities of protein phosphorylation in plants and review the current knowledge on phosphorylation-dependent regulation of plant chromatin and chromatin-associated proteins. We also outline some future challenges to further elucidate protein phosphorylation and chromatin regulation.

  14. Chromatin Pioneers | Center for Cancer Research

    Science.gov (United States)

    Taking advantage of their ability to explore provocative ideas, NCI investigators pioneered the study of chromatin to demonstrate its functional importance and lay the groundwork for understanding its role in cancer and other diseases.

  15. Replicating chromatin: a tale of histones

    DEFF Research Database (Denmark)

    Groth, Anja

    2009-01-01

    Chromatin serves structural and functional roles crucial for genome stability and correct gene expression. This organization must be reproduced on daughter strands during replication to maintain proper overlay of epigenetic fabric onto genetic sequence. Nucleosomes constitute the structural...... framework of chromatin and carry information to specify higher-order organization and gene expression. When replication forks traverse the chromosomes, nucleosomes are transiently disrupted, allowing the replication machinery to gain access to DNA. Histone recycling, together with new deposition, ensures...

  16. Synaptic, transcriptional and chromatin genes disrupted in autism.

    Science.gov (United States)

    De Rubeis, Silvia; He, Xin; Goldberg, Arthur P; Poultney, Christopher S; Samocha, Kaitlin; Cicek, A Erucment; Kou, Yan; Liu, Li; Fromer, Menachem; Walker, Susan; Singh, Tarinder; Klei, Lambertus; Kosmicki, Jack; Shih-Chen, Fu; Aleksic, Branko; Biscaldi, Monica; Bolton, Patrick F; Brownfeld, Jessica M; Cai, Jinlu; Campbell, Nicholas G; Carracedo, Angel; Chahrour, Maria H; Chiocchetti, Andreas G; Coon, Hilary; Crawford, Emily L; Curran, Sarah R; Dawson, Geraldine; Duketis, Eftichia; Fernandez, Bridget A; Gallagher, Louise; Geller, Evan; Guter, Stephen J; Hill, R Sean; Ionita-Laza, Juliana; Jimenz Gonzalez, Patricia; Kilpinen, Helena; Klauck, Sabine M; Kolevzon, Alexander; Lee, Irene; Lei, Irene; Lei, Jing; Lehtimäki, Terho; Lin, Chiao-Feng; Ma'ayan, Avi; Marshall, Christian R; McInnes, Alison L; Neale, Benjamin; Owen, Michael J; Ozaki, Noriio; Parellada, Mara; Parr, Jeremy R; Purcell, Shaun; Puura, Kaija; Rajagopalan, Deepthi; Rehnström, Karola; Reichenberg, Abraham; Sabo, Aniko; Sachse, Michael; Sanders, Stephan J; Schafer, Chad; Schulte-Rüther, Martin; Skuse, David; Stevens, Christine; Szatmari, Peter; Tammimies, Kristiina; Valladares, Otto; Voran, Annette; Li-San, Wang; Weiss, Lauren A; Willsey, A Jeremy; Yu, Timothy W; Yuen, Ryan K C; Cook, Edwin H; Freitag, Christine M; Gill, Michael; Hultman, Christina M; Lehner, Thomas; Palotie, Aaarno; Schellenberg, Gerard D; Sklar, Pamela; State, Matthew W; Sutcliffe, James S; Walsh, Christiopher A; Scherer, Stephen W; Zwick, Michael E; Barett, Jeffrey C; Cutler, David J; Roeder, Kathryn; Devlin, Bernie; Daly, Mark J; Buxbaum, Joseph D

    2014-11-13

    The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.

  17. DNA damage-induced inflammation and nuclear architecture.

    Science.gov (United States)

    Stratigi, Kalliopi; Chatzidoukaki, Ourania; Garinis, George A

    2017-07-01

    Nuclear architecture and the chromatin state affect most-if not all- DNA-dependent transactions, including the ability of cells to sense DNA lesions and restore damaged DNA back to its native form. Recent evidence points to functional links between DNA damage sensors, DNA repair mechanisms and the innate immune responses. The latter raises the question of how such seemingly disparate processes operate within the intrinsically complex nuclear landscape and the chromatin environment. Here, we discuss how DNA damage-induced immune responses operate within chromatin and the distinct sub-nuclear compartments highlighting their relevance to chronic inflammation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Architectural slicing

    DEFF Research Database (Denmark)

    Christensen, Henrik Bærbak; Hansen, Klaus Marius

    2013-01-01

    Architectural prototyping is a widely used practice, con- cerned with taking architectural decisions through experiments with light- weight implementations. However, many architectural decisions are only taken when systems are already (partially) implemented. This is prob- lematic in the context...... of architectural prototyping since experiments with full systems are complex and expensive and thus architectural learn- ing is hindered. In this paper, we propose a novel technique for harvest- ing architectural prototypes from existing systems, \\architectural slic- ing", based on dynamic program slicing. Given...... a system and a slicing criterion, architectural slicing produces an architectural prototype that contain the elements in the architecture that are dependent on the ele- ments in the slicing criterion. Furthermore, we present an initial design and implementation of an architectural slicer for Java....

  19. Repression of germline RNAi pathways in somatic cells by retinoblastoma pathway chromatin complexes.

    Directory of Open Access Journals (Sweden)

    Xiaoyun Wu

    Full Text Available The retinoblastoma (Rb tumor suppressor acts with a number of chromatin cofactors in a wide range of species to suppress cell proliferation. The Caenorhabditis elegans retinoblastoma gene and many of these cofactors, called synMuv B genes, were identified in genetic screens for cell lineage defects caused by growth factor misexpression. Mutations in many synMuv B genes, including lin-35/Rb, also cause somatic misexpression of the germline RNA processing P granules and enhanced RNAi. We show here that multiple small RNA components, including a set of germline-specific Argonaute genes, are misexpressed in the soma of many synMuv B mutant animals, revealing one node for enhanced RNAi. Distinct classes of synMuv B mutants differ in the subcellular architecture of their misexpressed P granules, their profile of misexpressed small RNA and P granule genes, as well as their enhancement of RNAi and the related silencing of transgenes. These differences define three classes of synMuv B genes, representing three chromatin complexes: a LIN-35/Rb-containing DRM core complex, a SUMO-recruited Mec complex, and a synMuv B heterochromatin complex, suggesting that intersecting chromatin pathways regulate the repression of small RNA and P granule genes in the soma and the potency of RNAi. Consistent with this, the DRM complex and the synMuv B heterochromatin complex were genetically additive and displayed distinct antagonistic interactions with the MES-4 histone methyltransferase and the MRG-1 chromodomain protein, two germline chromatin regulators required for the synMuv phenotype and the somatic misexpression of P granule components. Thus intersecting synMuv B chromatin pathways conspire with synMuv B suppressor chromatin factors to regulate the expression of small RNA pathway genes, which enables heightened RNAi response. Regulation of small RNA pathway genes by human retinoblastoma may also underlie its role as a tumor suppressor gene.

  20. From the chromatin interaction network to the organization of the human genome into replication N/U-domains

    International Nuclear Information System (INIS)

    Boulos, Rasha E; Julienne, Hanna; Baker, Antoine; Jensen, Pablo; Arneodo, Alain; Audit, Benjamin; Chen, Chun-Long; D'Aubenton-Carafa, Yves; Thermes, Claude; Petryk, Nataliya; Kahli, Malik; Hyrien, Olivier; Goldar, Arach

    2014-01-01

    The three-dimensional (3D) architecture of the mammalian nucleus is now being unraveled thanks to the recent development of chromatin conformation capture (3C) technologies. Here we report the results of a combined multiscale analysis of genome-wide mean replication timing and chromatin conformation data that reveal some intimate relationships between chromatin folding and human DNA replication. We previously described megabase replication N/U-domains as mammalian multiorigin replication units, and showed that their borders are ‘master’ replication initiation zones that likely initiate cascades of origin firing responsible for the stereotypic replication of these domains. Here, we demonstrate that replication N/U-domains correspond to the structural domains of self-interacting chromatin, and that their borders act as insulating regions both in high-throughput 3C (Hi-C) data and high-resolution 3C (4C) experiments. Further analyses of Hi-C data using a graph-theoretical approach reveal that N/U-domain borders are long-distance, interconnected hubs of the chromatin interaction network. Overall, these results and the observation that a well-defined ordering of chromatin states exists from N/U-domain borders to centers suggest that ‘master’ replication initiation zones are at the heart of a high-order, epigenetically controlled 3D organization of the human genome. (paper)

  1. Neutron-scattering studies of chromatin

    International Nuclear Information System (INIS)

    Bradbury, E.M.; Baldwin, J.P.; Carpenter, B.G.; Hjelm, R.P.; Hancock, R.; Ibel, K.

    1976-01-01

    It is clear that a knowledge of the basic molecular structure of chromatin is a prerequisite for any progress toward an understanding of chromosome organization. With a two-component system, protein and nucleic acid, neutrons have a particularly powerful application to studies of the spatial arrangements of these components because of the ability, by contrast matching with H 2 O-D 2 O mixtures, to obtain neutron-scattering data on the individual components. With this approach it has been shown that the neutron diffraction of chromatin is consistent with a ''beads on a string'' model in which the bead consists of a protein core with DNA coiled on the outside. However, because chromatin is a gel and gives limited structural data, confirmation of such a model requires extension of the neutron studies by deuteration of specific chromatin components and the isolation of chromatin subunits. Although these studies are not complete, the neutron results so far obtained support the subunit model described above

  2. New mitotic regulators released from chromatin

    Directory of Open Access Journals (Sweden)

    Hideki eYokoyama

    2013-12-01

    Full Text Available Faithful action of the mitotic spindle segregates duplicated chromosomes into daughter cells. Perturbations of this process result in chromosome mis-segregation, leading to chromosomal instability and cancer development. Chromosomes are not simply passengers segregated by spindle microtubules but rather play a major active role in spindle assembly. The GTP bound form of the Ran GTPase (RanGTP, produced around chromosomes, locally activates spindle assembly factors. Recent studies have uncovered that chromosomes organize mitosis beyond spindle formation. They distinctly regulate other mitotic events, such as spindle maintenance in anaphase, which is essential for chromosome segregation. Furthermore, the direct function of chromosomes is not only to produce RanGTP but, in addition, to release key mitotic regulators from chromatin. Chromatin-remodeling factors and nuclear pore complex proteins, which have established functions on chromatin in interphase, dissociate from mitotic chromatin and function in spindle assembly or maintenance. Thus, chromosomes actively organize their own segregation using chromatin-releasing mitotic regulators as well as RanGTP.

  3. Map of open and closed chromatin domains in Drosophila genome.

    Science.gov (United States)

    Milon, Beatrice; Sun, Yezhou; Chang, Weizhong; Creasy, Todd; Mahurkar, Anup; Shetty, Amol; Nurminsky, Dmitry; Nurminskaya, Maria

    2014-11-18

    Chromatin compactness has been considered a major determinant of gene activity and has been associated with specific chromatin modifications in studies on a few individual genetic loci. At the same time, genome-wide patterns of open and closed chromatin have been understudied, and are at present largely predicted from chromatin modification and gene expression data. However the universal applicability of such predictions is not self-evident, and requires experimental verification. We developed and implemented a high-throughput analysis for general chromatin sensitivity to DNase I which provides a comprehensive epigenomic assessment in a single assay. Contiguous domains of open and closed chromatin were identified by computational analysis of the data, and correlated to other genome annotations including predicted chromatin "states", individual chromatin modifications, nuclear lamina interactions, and gene expression. While showing that the widely trusted predictions of chromatin structure are correct in the majority of cases, we detected diverse "exceptions" from the conventional rules. We found a profound paucity of chromatin modifications in a major fraction of closed chromatin, and identified a number of loci where chromatin configuration is opposite to that expected from modification and gene expression patterns. Further, we observed that chromatin of large introns tends to be closed even when the genes are expressed, and that a significant proportion of active genes including their promoters are located in closed chromatin. These findings reveal limitations of the existing predictive models, indicate novel mechanisms of epigenetic regulation, and provide important insights into genome organization and function.

  4. Autism genes keep turning up chromatin.

    Science.gov (United States)

    Lasalle, Janine M

    2013-06-19

    Autism-spectrum disorders (ASD) are complex genetic disorders collectively characterized by impaired social interactions and language as well as repetitive and restrictive behaviors. Of the hundreds of genes implicated in ASD, those encoding proteins acting at neuronal synapses have been most characterized by candidate gene studies. However, recent unbiased genome-wide analyses have turned up a multitude of novel candidate genes encoding nuclear factors implicated in chromatin remodeling, histone demethylation, histone variants, and the recognition of DNA methylation. Furthermore, the chromatin landscape of the human genome has been shown to influence the location of de novo mutations observed in ASD as well as the landscape of DNA methylation underlying neurodevelopmental and synaptic processes. Understanding the interactions of nuclear chromatin proteins and DNA with signal transduction pathways and environmental influences in the developing brain will be critical to understanding the relevance of these ASD candidate genes and continued uncovering of the "roots" of autism etiology.

  5. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components

    DEFF Research Database (Denmark)

    Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Po

    2014-01-01

    To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use nascent chromatin capture (NCC) to profile chromatin proteome dynamics during...... replication in human cells. NCC relies on biotin-dUTP labelling of replicating DNA, affinity purification and quantitative proteomics. Comparing nascent chromatin with mature post-replicative chromatin, we provide association dynamics for 3,995 proteins. The replication machinery and 485 chromatin factors...... such as CAF-1, DNMT1 and SUV39h1 are enriched in nascent chromatin, whereas 170 factors including histone H1, DNMT3, MBD1-3 and PRC1 show delayed association. This correlates with H4K5K12diAc removal and H3K9me1 accumulation, whereas H3K27me3 and H3K9me3 remain unchanged. Finally, we combine NCC enrichment...

  6. CHD chromatin remodelers and the transcription cycle

    Science.gov (United States)

    Murawska, Magdalena

    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 also 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. PMID:22223048

  7. Chromatin proteins and modifications as drug targets

    DEFF Research Database (Denmark)

    Helin, Kristian; Dhanak, Dashyant

    2013-01-01

    A plethora of groundbreaking studies have demonstrated the importance of chromatin-associated proteins and post-translational modifications of histones, proteins and DNA (so-called epigenetic modifications) for transcriptional control and normal development. Disruption of epigenetic control...... is a frequent event in disease, and the first epigenetic-based therapies for cancer treatment have been approved. A generation of new classes of potent and specific inhibitors for several chromatin-associated proteins have shown promise in preclinical trials. Although the biology of epigenetic regulation...

  8. Modulation of chromatin access during adipocyte differentiation

    DEFF Research Database (Denmark)

    Mandrup, Susanne; Hager, Gordon L

    2012-01-01

    identified; however, it is not until recently that we have begun to understand how these factors act at a genome-wide scale. In a recent publication we have mapped the genome-wide changes in chromatin structure during differentiation of 3T3-L1 preadipocytes and shown that a major reorganization...... of the chromatin landscape occurs within few hours following the addition of the adipogenic cocktail. In addition, we have mapped the genome-wide profiles of several of the early adipogenic transcription factors and shown that they act in a highly cooperative manner to drive this dramatic remodeling process....

  9. Dynamics of Histone Tails within Chromatin

    Science.gov (United States)

    Bernier, Morgan; North, Justin; Page, Michael; Jaroniec, Christopher; Hammel, Christopher; Poirier, Michael

    2012-02-01

    Genetic information in humans is encoded within DNA molecules that is wrapped around histone octamer proteins and compacted into a highly conserved structural polymer, chromatin. The physical and material properties of chromatin appear to influence gene expression by altering the accessibility of proteins to the DNA. The tails of the histones are flexible domains that are thought to play a role in regulating DNA accessibility and compaction; however the molecular mechanisms for these phenomena are not understood. I will present CW-EPR studies on site directed spin labeled nucleosomes that probe the structure and dynamics of these histone tails within nucleosomes.

  10. Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin

    Energy Technology Data Exchange (ETDEWEB)

    Illner, Doris; Zinner, Roman; Handtke, Violet; Rouquette, Jacques; Strickfaden, Hilmar [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Lanctot, Christian [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Institute of Cellular Biology and Pathology, Charles University Prague (Czech Republic); Conrad, Marcus; Seiler, Alexander [Helmholtz Zentrum Munich, Institute of Clinical Molecular Biology and Tumor Genetics, Marchioninistr. 25, 81377 Munich (Germany); Imhof, Axel [Adolf Butenandt Institute, Department of Molecular Biology (Germany); Munich Center for Integrated Protein Sciences (CIPSM), 81377 Munich (Germany); Cremer, Thomas [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany); Munich Center for Integrated Protein Sciences (CIPSM), 81377 Munich (Germany); Cremer, Marion, E-mail: Marion.Cremer@lrz.uni-muenchen.de [Biozentrum, Department of Biology II (Chair of Anthropology and Human Genetics), Ludwig-Maximilians-University, Grosshadernerstrasse 2, 82152 Martinsried (Germany)

    2010-06-10

    Extensive changes of higher order chromatin arrangements can be observed during prometaphase, terminal cell differentiation and cellular senescence. Experimental systems where major reorganization of nuclear architecture can be induced under defined conditions, may help to better understand the functional implications of such changes. Here, we report on profound chromatin reorganization in fibroblast nuclei by chaetocin, a thiodioxopiperazine metabolite. Chaetocin induces strong condensation of chromosome territories separated by a wide interchromatin space largely void of DNA. Cell viability is maintained irrespective of this peculiar chromatin phenotype. Cell cycle markers, histone signatures, and tests for cellular senescence and for oxidative stress indicate that chaetocin induced chromatin condensation/clustering (CICC) represents a distinct entity among nuclear phenotypes associated with condensed chromatin. The territorial organization of entire chromosomes is maintained in CICC nuclei; however, the conventional nuclear architecture harboring gene-dense chromatin in the nuclear interior and gene-poor chromatin at the nuclear periphery is lost. Instead gene-dense and transcriptionally active chromatin is shifted to the periphery of individual condensed chromosome territories where nascent RNA becomes highly enriched around their outer surface. This chromatin reorganization makes CICC nuclei an attractive model system to study this border zone as a distinct compartment for transcription. Induction of CICC is fully inhibited by thiol-dependent antioxidants, but is not related to the production of reactive oxygen species. Our results suggest that chaetocin functionally impairs the thioredoxin (Trx) system, which is essential for deoxynucleotide synthesis, but in addition involved in a wide range of cellular functions. The mechanisms involved in CICC formation remain to be fully explored.

  11. Remodeling of nuclear architecture by the thiodioxoxpiperazine metabolite chaetocin

    International Nuclear Information System (INIS)

    Illner, Doris; Zinner, Roman; Handtke, Violet; Rouquette, Jacques; Strickfaden, Hilmar; Lanctot, Christian; Conrad, Marcus; Seiler, Alexander; Imhof, Axel; Cremer, Thomas; Cremer, Marion

    2010-01-01

    Extensive changes of higher order chromatin arrangements can be observed during prometaphase, terminal cell differentiation and cellular senescence. Experimental systems where major reorganization of nuclear architecture can be induced under defined conditions, may help to better understand the functional implications of such changes. Here, we report on profound chromatin reorganization in fibroblast nuclei by chaetocin, a thiodioxopiperazine metabolite. Chaetocin induces strong condensation of chromosome territories separated by a wide interchromatin space largely void of DNA. Cell viability is maintained irrespective of this peculiar chromatin phenotype. Cell cycle markers, histone signatures, and tests for cellular senescence and for oxidative stress indicate that chaetocin induced chromatin condensation/clustering (CICC) represents a distinct entity among nuclear phenotypes associated with condensed chromatin. The territorial organization of entire chromosomes is maintained in CICC nuclei; however, the conventional nuclear architecture harboring gene-dense chromatin in the nuclear interior and gene-poor chromatin at the nuclear periphery is lost. Instead gene-dense and transcriptionally active chromatin is shifted to the periphery of individual condensed chromosome territories where nascent RNA becomes highly enriched around their outer surface. This chromatin reorganization makes CICC nuclei an attractive model system to study this border zone as a distinct compartment for transcription. Induction of CICC is fully inhibited by thiol-dependent antioxidants, but is not related to the production of reactive oxygen species. Our results suggest that chaetocin functionally impairs the thioredoxin (Trx) system, which is essential for deoxynucleotide synthesis, but in addition involved in a wide range of cellular functions. The mechanisms involved in CICC formation remain to be fully explored.

  12. Chromatin damage induced by fast neutrons or UV laser radiation

    Energy Technology Data Exchange (ETDEWEB)

    Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I

    2002-07-01

    Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m{sup -2}. The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

  13. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templates

    National Research Council Canada - National Science Library

    Nordeen, Steven

    2000-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  14. Classical and Nonclassical Estrogen Receptor Action on Chromatin Templaces

    National Research Council Canada - National Science Library

    Nordeen, Steve

    2001-01-01

    .... Using newly-developed approaches, I investigated mechanisms of estrogen/estrogen receptor action on chromatin templates in vitro in order to better understand the role of chromatin in steroid-regulated gene expression...

  15. Chromatin Repressive Complexes in Stem Cells, Development, and Cancer

    DEFF Research Database (Denmark)

    Laugesen, Anne; Helin, Kristian

    2014-01-01

    The chromatin environment is essential for the correct specification and preservation of cell identity through modulation and maintenance of transcription patterns. Many chromatin regulators are required for development, stem cell maintenance, and differentiation. Here, we review the roles...

  16. Chromatin damage induced by fast neutrons or UV laser radiation

    International Nuclear Information System (INIS)

    Radu, L.; Constantinescu, B.; Gazdaru, D.; Mihailescu, I.

    2002-01-01

    Chromatin samples from livers of Wistar rats were subjected to fast neutron irradiation in doses of 10-100 Gy or to a 248 nm excimer laser radiation, in doses of 0.5-3 MJ.m -2 . The action of the radiation on chromatin was monitored by chromatin intrinsic fluorescence and fluorescence lifetimes (of bound ethidium bromide to chromatin) and by analysing fluorescence resonance energy transfer between dansyl chloride and acridine orange coupled to chromatin. For the mentioned doses of UV excimer laser radiation, the action on chromatin was more intense than in the case of fast neutrons. The same types of damage are produced by the two radiations: acidic and basic destruction of chromatin protein structure, DNA strand breaking and the increase of the distance between DNA and proteins in chromatin. (author)

  17. Local Nucleosome Dynamics Facilitate Chromatin Accessibility in Living Mammalian Cells

    Directory of Open Access Journals (Sweden)

    Saera Hihara

    2012-12-01

    Full Text Available Genome information, which is three-dimensionally organized within cells as chromatin, is searched and read by various proteins for diverse cell functions. Although how the protein factors find their targets remains unclear, the dynamic and flexible nature of chromatin is likely crucial. Using a combined approach of fluorescence correlation spectroscopy, single-nucleosome imaging, and Monte Carlo computer simulations, we demonstrate local chromatin dynamics in living mammalian cells. We show that similar to interphase chromatin, dense mitotic chromosomes also have considerable chromatin accessibility. For both interphase and mitotic chromatin, we observed local fluctuation of individual nucleosomes (∼50 nm movement/30 ms, which is caused by confined Brownian motion. Inhibition of these local dynamics by crosslinking impaired accessibility in the dense chromatin regions. Our findings show that local nucleosome dynamics drive chromatin accessibility. We propose that this local nucleosome fluctuation is the basis for scanning genome information.

  18. Deoxyribonuclease probing of sea urchin embryo chromatin

    International Nuclear Information System (INIS)

    Landsman, D.

    1983-01-01

    The role that the sea urchin, Parechinus angulosus, embryo and sperm histone variants plays in chromatin structure has been investigated. Chromatin structure has been determined at different levels of resolution in sperm and in developing embryos using micrococcal nuclease, pancreatic deoxyribonuclease (DNase I) and restriction endonucleases. Micrococcal nuclease and restriction endonuclease digestions of sea urchin gastrula chromatin have been analysed and it is shown that it is not possible to isolate large polynucleosomal chromatin complexes which are soluble in low ionic strength buffers. The repeat length for sperm is significantly larger than blastula and gastrula repeat lengths whereas blastula and gastrula repeat lengths are not significantly different. Nucleosomal core particles have been isolated from early blastula, gastrula and sperm of sea urchins. After DNase I digestion of 5'-labelled core particles the rate constants of cutting of the DNA at the susceptible sites on these core particles have been determined. The DNase I digestion kinetics of blastula and gastrula core particles are similar whereas sperm core particles are digested at a slower rate, mainly at the sites which are closest to the ends of the core particle DNA

  19. Chromatin conformation capture strategies in molecular diagnostics

    NARCIS (Netherlands)

    de Vree, Pauline J.P.

    2015-01-01

    In this thesis I have explored the clinical potential of the 4C-technology and worked on development of a novel chromatin conformation capture based technology, called TLA. In chapter 2 I describe how the 4C-technology can be applied as a targeted strategy to identify putative fusion-genes or

  20. Chromatin organisation during Arabidopsis root development

    NARCIS (Netherlands)

    Lorvellec, M.

    2007-01-01

    The genetic information is stored in a highly compact manner in every nucleus. About 150 bp of DNA is packed around a histone octamer constituting a nucleosome. Nucleosomes are linked together by histone H1 and further compaction of this "beads on a string" form higher-order chromatin structures.

  1. Keystone Symposia on Epigenomics and Chromatin Dynamics

    DEFF Research Database (Denmark)

    Ravnskjær, Kim

    2012-01-01

    Keystone Symposia kicked off the start of 2012 with two joint meetings on Epigenomics and Chromatin Dynamics and a star-studded list of speakers. Held in Keystone, CO, January 17-22, and organized by Steven Jacobsen and Steven Henikoff and by Bradley Cairns and Geneviève Almouzni, respectively...

  2. The Latest Twists in Chromatin Remodeling.

    Science.gov (United States)

    Blossey, Ralf; Schiessel, Helmut

    2018-01-05

    In its most restrictive interpretation, the notion of chromatin remodeling refers to the action of chromatin-remodeling enzymes on nucleosomes with the aim of displacing and removing them from the chromatin fiber (the effective polymer formed by a DNA molecule and proteins). This local modification of the fiber structure can have consequences for the initiation and repression of the transcription process, and when the remodeling process spreads along the fiber, it also results in long-range effects essential for fiber condensation. There are three regulatory levels of relevance that can be distinguished for this process: the intrinsic sequence preference of the histone octamer, which rules the positioning of the nucleosome along the DNA, notably in relation to the genetic information coded in DNA; the recognition or selection of nucleosomal substrates by remodeling complexes; and, finally, the motor action on the nucleosome exerted by the chromatin remodeler. Recent work has been able to provide crucial insights at each of these three levels that add new twists to this exciting and unfinished story, which we highlight in this perspective. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Chromatin organization and cellular sensitivity to ionizing radiation

    International Nuclear Information System (INIS)

    Szumiel, I.; Walicka, M.

    1987-01-01

    The paper briefly describes chromatin organization in mammalian cells and reviews experimental work concerning relations between chromatin structure and accesibility of damaged DNA to repair enzymes. The ''contact effect'', the size of super-coiled DNA domains and ADP-ribosylation of chromatin proteins are discussed in relation to cellular radiosensitivity. 88 refs. (author)

  4. Chromatin Dynamics of the mouse β-globin locus

    NARCIS (Netherlands)

    M.P.C. van de Corput (Mariëtte); E. de Boer (Ernie); T.A. Knoch (Tobias); W.A. van Cappellen (Gert); M. Lesnussa (Michael); H.J.F.M.M. Eussen (Bert)

    2010-01-01

    textabstractLately it has become more clear that (subtle) changes in 3D organization of chromatin can either trigger transcription or silence genes or gene clusters. It has also been postulated that due to changes in chromatin structure, a change in chromatin accessibility of transcription factors

  5. Structural chromatin organization as a factor determining the rate of chromatin endonucleolysis in irradiated and intact thymocytes

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Ivannik, B.P.

    1987-01-01

    A study was made of chromatin endonucleolysis in hypotonized thymocytes incubating in digestive buffers containing different concentrations of potassium, magnesium, calcium, and mercaptoethanol. Inhibition of endonucleolysis by univalent cation during the first 20 min of incubation was followed by intensive chromatin degradation. A decrease in free potassium content retarded chromatin degradation and enhanced the inhibiting effect of the univalent cations. The regularities of changes in the rate of chromatin endonucleolysis in different digestive buffers were similar with both exposed and intact thymocytes

  6. MeCP2 Rett mutations affect large scale chromatin organization

    DEFF Research Database (Denmark)

    Gupta, Noopur Agarwal; Becker, Annette; Jost, K Laurence

    2011-01-01

    Rett syndrome is a neurological, X chromosomal-linked disorder associated with mutations in the MECP2 gene. MeCP2 protein has been proposed to play a role in transcriptional regulation as well as in chromatin architecture. Since MeCP2 mutant cells exhibit surprisingly mild changes in gene...... expression, we have now explored the possibility that Rett mutations may affect the ability of MeCP2 to bind and organize chromatin. We found that all but one of the 21 missense MeCP2 mutants analyzed accumulated at heterochromatin and about half of them were significantly affected. Furthermore, two......-thirds of all mutants showed a significantly decreased ability to cluster heterochromatin. Three mutants containing different proline substitutions (P101H, P101R and P152R) were severely affected only in heterochromatin clustering and located far away from the DNA interface in the MeCP2 methyl-binding domain...

  7. Robotic architectures

    CSIR Research Space (South Africa)

    Mtshali, M

    2010-01-01

    Full Text Available In the development of mobile robotic systems, a robotic architecture plays a crucial role in interconnecting all the sub-systems and controlling the system. The design of robotic architectures for mobile autonomous robots is a challenging...

  8. Architecture & Environment

    Science.gov (United States)

    Erickson, Mary; Delahunt, Michael

    2010-01-01

    Most art teachers would agree that architecture is an important form of visual art, but they do not always include it in their curriculums. In this article, the authors share core ideas from "Architecture and Environment," a teaching resource that they developed out of a long-term interest in teaching architecture and their fascination with the…

  9. Chromatin accessibility prediction via convolutional long short-term memory networks with k-mer embedding.

    Science.gov (United States)

    Min, Xu; Zeng, Wanwen; Chen, Ning; Chen, Ting; Jiang, Rui

    2017-07-15

    Experimental techniques for measuring chromatin accessibility are expensive and time consuming, appealing for the development of computational approaches to predict open chromatin regions from DNA sequences. Along this direction, existing methods fall into two classes: one based on handcrafted k -mer features and the other based on convolutional neural networks. Although both categories have shown good performance in specific applications thus far, there still lacks a comprehensive framework to integrate useful k -mer co-occurrence information with recent advances in deep learning. We fill this gap by addressing the problem of chromatin accessibility prediction with a convolutional Long Short-Term Memory (LSTM) network with k -mer embedding. We first split DNA sequences into k -mers and pre-train k -mer embedding vectors based on the co-occurrence matrix of k -mers by using an unsupervised representation learning approach. We then construct a supervised deep learning architecture comprised of an embedding layer, three convolutional layers and a Bidirectional LSTM (BLSTM) layer for feature learning and classification. We demonstrate that our method gains high-quality fixed-length features from variable-length sequences and consistently outperforms baseline methods. We show that k -mer embedding can effectively enhance model performance by exploring different embedding strategies. We also prove the efficacy of both the convolution and the BLSTM layers by comparing two variations of the network architecture. We confirm the robustness of our model to hyper-parameters by performing sensitivity analysis. We hope our method can eventually reinforce our understanding of employing deep learning in genomic studies and shed light on research regarding mechanisms of chromatin accessibility. The source code can be downloaded from https://github.com/minxueric/ismb2017_lstm . tingchen@tsinghua.edu.cn or ruijiang@tsinghua.edu.cn. Supplementary materials are available at

  10. HDAC up-regulation in early colon field carcinogenesis is involved in cell tumorigenicity through regulation of chromatin structure.

    Directory of Open Access Journals (Sweden)

    Yolanda Stypula-Cyrus

    Full Text Available Normal cell function is dependent on the proper maintenance of chromatin structure. Regulation of chromatin structure is controlled by histone modifications that directly influence chromatin architecture and genome function. Specifically, the histone deacetylase (HDAC family of proteins modulate chromatin compaction and are commonly dysregulated in many tumors, including colorectal cancer (CRC. However, the role of HDAC proteins in early colorectal carcinogenesis has not been previously reported. We found HDAC1, HDAC2, HDAC3, HDAC5, and HDAC7 all to be up-regulated in the field of human CRC. Furthermore, we observed that HDAC2 up-regulation is one of the earliest events in CRC carcinogenesis and observed this in human field carcinogenesis, the azoxymethane-treated rat model, and in more aggressive colon cancer cell lines. The universality of HDAC2 up-regulation suggests that HDAC2 up-regulation is a novel and important early event in CRC, which may serve as a biomarker. HDAC inhibitors (HDACIs interfere with tumorigenic HDAC activity; however, the precise mechanisms involved in this process remain to be elucidated. We confirmed that HDAC inhibition by valproic acid (VPA targeted the more aggressive cell line. Using nuclease digestion assays and transmission electron microscopy imaging, we observed that VPA treatment induced greater changes in chromatin structure in the more aggressive cell line. Furthermore, we used the novel imaging technique partial wave spectroscopy (PWS to quantify nanoscale alterations in chromatin. We noted that the PWS results are consistent with the biological assays, indicating a greater effect of VPA treatment in the more aggressive cell type. Together, these results demonstrate the importance of HDAC activity in early carcinogenic events and the unique role of higher-order chromatin structure in determining cell tumorigenicity.

  11. Poly(ADP-ribosyl)ation of Methyl CpG Binding Domain Protein 2 Regulates Chromatin Structure*

    Science.gov (United States)

    Becker, Annette; Zhang, Peng; Allmann, Lena; Meilinger, Daniela; Bertulat, Bianca; Eck, Daniel; Hofstaetter, Maria; Bartolomei, Giody; Hottiger, Michael O.; Schreiber, Valérie; Leonhardt, Heinrich; Cardoso, M. Cristina

    2016-01-01

    The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphorylation and other posttranslational modifications of MeCP2 have been described recently to modulate its function. Here we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue. Consequently, we found that MeCP2 induced aggregation of pericentric heterochromatin and that its chromatin accumulation was enhanced in poly(ADP-ribose) polymerase (PARP) 1−/− compared with wild-type cells. We mapped the poly(ADP-ribosyl)ation domains and engineered MeCP2 mutation constructs to further analyze potential effects on DNA binding affinity and large-scale chromatin remodeling. Single or double deletion of the poly(ADP-ribosyl)ated regions and PARP inhibition increased the heterochromatin clustering ability of MeCP2. Increased chromatin clustering may reflect increased binding affinity. In agreement with this hypothesis, we found that PARP-1 deficiency significantly increased the chromatin binding affinity of MeCP2 in vivo. These data provide novel mechanistic insights into the regulation of MeCP2-mediated, higher-order chromatin architecture and suggest therapeutic opportunities to manipulate MeCP2 function. PMID:26772194

  12. Chromatin Regulation of Neuronal Maturation and Plasticity.

    Science.gov (United States)

    Gallegos, David A; Chan, Urann; Chen, Liang-Fu; West, Anne E

    2018-05-01

    Neurons are dynamic cells that respond and adapt to stimuli throughout their long postmitotic lives. The structural and functional plasticity of neurons requires the regulated transcription of new gene products, and dysregulation of transcription in either the developing or adult brain impairs cognition. We discuss how mechanisms of chromatin regulation help to orchestrate the transcriptional programs that underlie the maturation of developing neurons and the plasticity of adult neurons. We review how chromatin regulation acts locally to modulate the expression of specific genes and more broadly to coordinate gene expression programs during transitions between cellular states. These data highlight the importance of epigenetic transcriptional mechanisms in postmitotic neurons. We suggest areas where emerging methods may advance understanding in the future. Copyright © 2018 Elsevier Ltd. All rights reserved.

  13. Histone chaperone networks shaping chromatin function

    DEFF Research Database (Denmark)

    Hammond, Colin; Strømme, Caroline Bianchi; Huang, Hongda

    2017-01-01

    and fate, which affects all chromosomal processes, including gene expression, chromosome segregation and genome replication and repair. Here, we review the distinct structural and functional properties of the expanding network of histone chaperones. We emphasize how chaperones cooperate in the histone...... chaperone network and via co-chaperone complexes to match histone supply with demand, thereby promoting proper nucleosome assembly and maintaining epigenetic information by recycling modified histones evicted from chromatin....

  14. Probing chromatin structure with nuclease sensitivity assays.

    Science.gov (United States)

    Gregory, R I; Khosla, S; Feil, R

    2001-01-01

    To further our understanding of genomic imprinting it will be essential to identify key control elements, and to investigate their regulation by both epigenetic modifications (such as DNA methylation) and trans-acting factors. So far, sequence elements that regulate parental allele-specific gene expression have been identified in a number of imprinted loci, either because of their differential DNA methylation or through functional studies in transgenic mice (1,2). A systematic search for allele-specific chromatin features constitutes an alternative strategy to identify elements that regulate imprinting. The validity of such an in vivo chromatin approach derives from the fact that in several known imprinting control-elements, a specialized organization of chromatin characterized by nuclease hypersensitivity is present on only one of the two parental chromosome (3). For example, the differentially methylated 5 -portion of the human SNRPN gene-a sequence element that controls imprinting in the Prader-Willi and Angelman syndromes' domain on chromosome 15q11- q13-has strong DNase-I hypersensitive sites on the unmethylated paternal chromosome (4). A differentially methylated region that regulates the imprinting of H19 and that of the neighboring insulin-like growth factor-2 gene on mouse chromosome 7 was also found to have parental chromosome-specific hypersensitive sites (5,6). The precise nature of the allelic nuclease hypersensitivity in these and other imprinted loci remains to be determined in more detail, for example, by applying complementary chromatin methodologies (7,8). However, it is commonly observed that a nuclease hypersensitive site corresponds to a small region where nucleosomes are absent or partially disrupted.

  15. [The biological aspects of chromatin diminution].

    Science.gov (United States)

    Akif'ev, A P; Grishanin, A K

    1993-01-01

    The chromatine diminution (CD), first discovered by Boveri (1887) in ascarids, represents programmed elimination of a part of genetic material in the nuclei of the somatic cells in cyclops and ascarids, and in the protist macronuclei. The CD can be considered as a macromutation sharply changing chromosomal structure, though minimally effecting the phenotype. The analysis of CD is of significance for discussing mechanisms of origin of chromosomal organization, transformation of genome molecular structure in eucaryote evolution, role of the extra DNA.

  16. Arabidopsis chromatin-associated HMGA and HMGB use different nuclear targeting signals and display highly dynamic localization within the nucleus

    DEFF Research Database (Denmark)

    Launholt, Dorte; Merkle, Thomas; Houben, Andreas

    2006-01-01

    In plants, the chromatin-associated high mobility group (HMG) proteins occur in twosubfamilies termedHMGAandHMGB.The HMGAproteins are characterized by the presence of four AT-hookDNAbinding motifs, and theHMGBproteins contain anHMG boxDNAbinding domain. As architectural factors, theHMGproteins ap......In plants, the chromatin-associated high mobility group (HMG) proteins occur in twosubfamilies termedHMGAandHMGB.The HMGAproteins are characterized by the presence of four AT-hookDNAbinding motifs, and theHMGBproteins contain anHMG boxDNAbinding domain. As architectural factors, the...... of interphase nuclei, whereas none of the proteins associate with condensed mitotic chromosomes. HMGA is targeted to the nucleus by a monopartite nuclear localization signal, while efficient nuclear accumulation of HMGB1/5 requires large portions of the basic N-terminal part of the proteins. The acidic C...

  17. Default assembly of early adenovirus chromatin

    International Nuclear Information System (INIS)

    Spector, David J.

    2007-01-01

    In adenovirus particles, the viral nucleoprotein is organized into a highly compacted core structure. Upon delivery to the nucleus, the viral nucleoprotein is very likely to be remodeled to a form accessible to the transcription and replication machinery. Viral protein VII binds to intra-nuclear viral DNA, as do at least two cellular proteins, SET/TAF-Iβ and pp32, components of a chromatin assembly complex that is implicated in template remodeling. We showed previously that viral DNA-protein complexes released from infecting particles were sensitive to shearing after cross-linking with formaldehyde, presumably after transport of the genome into the nucleus. We report here the application of equilibrium-density gradient centrifugation to the analysis of the fate of these complexes. Most of the incoming protein VII was recovered in a form that was not cross-linked to viral DNA. This release of protein VII, as well as the binding of SET/TAF-Iβ and cellular transcription factors to the viral chromatin, did not require de novo viral gene expression. The distinct density profiles of viral DNA complexes containing protein VII, compared to those containing SET/TAF-Iβ or transcription factors, were consistent with the notion that the assembly of early viral chromatin requires both the association of SET/TAF-1β and the release of protein VII

  18. Titration and hysteresis in epigenetic chromatin silencing

    International Nuclear Information System (INIS)

    Dayarian, Adel; Sengupta, Anirvan M

    2013-01-01

    Epigenetic mechanisms of silencing via heritable chromatin modifications play a major role in gene regulation and cell fate specification. We consider a model of epigenetic chromatin silencing in budding yeast and study the bifurcation diagram and characterize the bistable and the monostable regimes. The main focus of this paper is to examine how the perturbations altering the activity of histone modifying enzymes affect the epigenetic states. We analyze the implications of having the total number of silencing proteins, given by the sum of proteins bound to the nucleosomes and the ones available in the ambient, to be constant. This constraint couples different regions of chromatin through the shared reservoir of ambient silencing proteins. We show that the response of the system to perturbations depends dramatically on the titration effect caused by the above constraint. In particular, for a certain range of overall abundance of silencing proteins, the hysteresis loop changes qualitatively with certain jump replaced by continuous merger of different states. In addition, we find a nonmonotonic dependence of gene expression on the rate of histone deacetylation activity of Sir2. We discuss how these qualitative predictions of our model could be compared with experimental studies of the yeast system under anti-silencing drugs. (paper)

  19. Spectroscopic study of fast-neutron-irradiated chromatin

    International Nuclear Information System (INIS)

    Radu, L.; Gazdaru, D.; Constantinescu, B.

    2004-01-01

    The effects produced by fast neutrons (0-100 Gy) on chromatin structure were analyzed by (i) [ 1 H]-NMR spectroscopy, (ii) time resolved spectroscopy, and (iii) fluorescence resonance energy transfer (FRET). Two types of chromatin were tested: (i) a chromatin from a normal tissue (liver of Wistar rats) and (ii) a chromatin from a tumoral tissue (Guerin limphotrope epithelioma, a rat solid tumor). The fast-neutron action on chromatin determines greater values of the [ 1 H]-NMR transverse relaxation time, indicating a more injured structure. Time-resolved fluorescence measurements show that the relative contribution of the excited state lifetime of bound ethidium bromide to chromatin DNA diminishes with increasing irradiation doses. This reflects the damage that occurs in DNA structure: production of single- and double-strand breaks due to sugar and base modifications. By the FRET method, the distance between dansyl chloride and acridine orange coupled at chromatin was determined. This distance increases upon fast-neutron action. The radiosensitivity of the tumor tissue chromatin seems higher than that of the normal tissue chromatin, probably because of its higher (loose) euchromatin/(compact) heterochromatin ratio. As the values of the physical parameters analyzed are specific for a determined dose, the establishment of these parameters may constitute a criterion for the microdosimetry of chromatin radiolesions produced by fast neutrons. (author)

  20. Spectroscopic study of fast-neutron-irradiated chromatin

    Energy Technology Data Exchange (ETDEWEB)

    Radu, L. [V. Babes National Inst., Dept. of Molecular Genetics, Bucharest (Romania)]. E-mail: serbanradu@pcnet.ro; Gazdaru, D. [Bucharest Univ., Dept. of Biophysics, Physics Faculty, Bucharest (Romania); Constantinescu, B. [H. Hulubei National Inst., Dept. of Cyclotron, Bucharest (Romania)

    2004-02-01

    The effects produced by fast neutrons (0-100 Gy) on chromatin structure were analyzed by (i) [{sup 1}H]-NMR spectroscopy, (ii) time resolved spectroscopy, and (iii) fluorescence resonance energy transfer (FRET). Two types of chromatin were tested: (i) a chromatin from a normal tissue (liver of Wistar rats) and (ii) a chromatin from a tumoral tissue (Guerin limphotrope epithelioma, a rat solid tumor). The fast-neutron action on chromatin determines greater values of the [{sup 1}H]-NMR transverse relaxation time, indicating a more injured structure. Time-resolved fluorescence measurements show that the relative contribution of the excited state lifetime of bound ethidium bromide to chromatin DNA diminishes with increasing irradiation doses. This reflects the damage that occurs in DNA structure: production of single- and double-strand breaks due to sugar and base modifications. By the FRET method, the distance between dansyl chloride and acridine orange coupled at chromatin was determined. This distance increases upon fast-neutron action. The radiosensitivity of the tumor tissue chromatin seems higher than that of the normal tissue chromatin, probably because of its higher (loose) euchromatin/(compact) heterochromatin ratio. As the values of the physical parameters analyzed are specific for a determined dose, the establishment of these parameters may constitute a criterion for the microdosimetry of chromatin radiolesions produced by fast neutrons. (author)

  1. The chromatin remodeler SPLAYED regulates specific stress signaling pathways.

    Directory of Open Access Journals (Sweden)

    Justin W Walley

    2008-12-01

    Full Text Available Organisms are continuously exposed to a myriad of environmental stresses. Central to an organism's survival is the ability to mount a robust transcriptional response to the imposed stress. An emerging mechanism of transcriptional control involves dynamic changes in chromatin structure. Alterations in chromatin structure are brought about by a number of different mechanisms, including chromatin modifications, which covalently modify histone proteins; incorporation of histone variants; and chromatin remodeling, which utilizes ATP hydrolysis to alter histone-DNA contacts. While considerable insight into the mechanisms of chromatin remodeling has been gained, the biological role of chromatin remodeling complexes beyond their function as regulators of cellular differentiation and development has remained poorly understood. Here, we provide genetic, biochemical, and biological evidence for the critical role of chromatin remodeling in mediating plant defense against specific biotic stresses. We found that the Arabidopsis SWI/SNF class chromatin remodeling ATPase SPLAYED (SYD is required for the expression of selected genes downstream of the jasmonate (JA and ethylene (ET signaling pathways. SYD is also directly recruited to the promoters of several of these genes. Furthermore, we show that SYD is required for resistance against the necrotrophic pathogen Botrytis cinerea but not the biotrophic pathogen Pseudomonas syringae. These findings demonstrate not only that chromatin remodeling is required for selective pathogen resistance, but also that chromatin remodelers such as SYD can regulate specific pathways within biotic stress signaling networks.

  2. Chromosome aberration model combining radiation tracks, chromatin structure, DSB repair and chromatin mobility

    International Nuclear Information System (INIS)

    Friedland, W.; Kundrat, P.

    2015-01-01

    The module that simulates the kinetics and yields of radiation-induced chromosome aberrations within the biophysical code PARTRAC is described. Radiation track structures simulated by Monte Carlo methods are overlapped with multi-scale models of DNA and chromatin to assess the resulting DNA damage. Spatial mobility of individual DNA ends from double-strand breaks is modelled simultaneously with their processing by the non-homologous end-joining enzymes. To score diverse types of chromosome aberrations, the joined ends are classified regarding their original chromosomal location, orientation and the involvement of centromeres. A comparison with experimental data on dicentrics induced by gamma and alpha particles shows that their relative dose dependence is predicted correctly, although the absolute yields are overestimated. The critical model assumptions on chromatin mobility and on the initial damage recognition and chromatin remodelling steps and their future refinements to solve this issue are discussed. (authors)

  3. First Exon Length Controls Active Chromatin Signatures and Transcription

    Directory of Open Access Journals (Sweden)

    Nicole I. Bieberstein

    2012-07-01

    Full Text Available Here, we explore the role of splicing in transcription, employing both genome-wide analysis of human ChIP-seq data and experimental manipulation of exon-intron organization in transgenic cell lines. We show that the activating histone modifications H3K4me3 and H3K9ac map specifically to first exon-intron boundaries. This is surprising, because these marks help recruit general transcription factors (GTFs to promoters. In genes with long first exons, promoter-proximal levels of H3K4me3 and H3K9ac are greatly reduced; consequently, GTFs and RNA polymerase II are low at transcription start sites (TSSs and exhibit a second, promoter-distal peak from which transcription also initiates. In contrast, short first exons lead to increased H3K4me3 and H3K9ac at promoters, higher expression levels, accuracy in TSS usage, and a lower frequency of antisense transcription. Therefore, first exon length is predictive for gene activity. Finally, splicing inhibition and intron deletion reduce H3K4me3 levels and transcriptional output. Thus, gene architecture and splicing determines transcription quantity and quality as well as chromatin signatures.

  4. Vacuum ultraviolet (VUV) absorption spectra of chromatin and its components

    International Nuclear Information System (INIS)

    Dodonova, N.Y.; Kiseleva, M.N.; Petrov, M.Y.; Tsyganenko, N.M.; Bubyakina, V.V.; Chikhirzhina, G.I.

    1984-01-01

    The electron absorption spectra of thin films of chromatin and chromatin components in the ultraviolet region (140-280 nm) were investigated. The absorption coefficients μ(lambda) of chromatin, nucleosomes with and without histone H1, total histones (TH), and DNA were compared. The spectra of nucleosomes differ from the sum-spectrum of DNA plus TH. The chromatin and nucleosome spectra are not similar in the spectral region of 190-160 nm. The lack of additivity of absorption coefficients at different wavelengths may be explained by different conformational changes of DNA, TH in nucleosomes and chromatin during the process of drying aqueous solutions for the preparation of thin films. The μ(lambda) values are useful for an estimate of the DNA and TH absorption in chromatin and nucleosomes in discussing UV and VUV irradiation damages. (Auth.)

  5. Vibrational energy relaxation: proposed pathway of fast local chromatin denaturation

    International Nuclear Information System (INIS)

    Harder, D.; Greinert, R.

    2002-01-01

    The molecular mechanism responsible for the a component of exchange-type chromosome aberrations, of chromosome fragmentation and of reproductive cell death is one of the unsolved issues of radiation biology. Under review is whether vibrational energy relaxation in the constitutive biopolymers of chromatin, induced by inelastic energy deposition events and mediated via highly excited vibrational states, may provide a pathway of fast local chromatin denaturation, thereby producing the severe DNA lesion able to interact chemically with other, non-damaged chromatin. (author)

  6. Architectural Contestation

    NARCIS (Netherlands)

    Merle, J.

    2012-01-01

    This dissertation addresses the reductive reading of Georges Bataille's work done within the field of architectural criticism and theory which tends to set aside the fundamental ‘broken’ totality of Bataille's oeuvre and also to narrowly interpret it as a mere critique of architectural form,

  7. Architecture Sustainability

    NARCIS (Netherlands)

    Avgeriou, Paris; Stal, Michael; Hilliard, Rich

    2013-01-01

    Software architecture is the foundation of software system development, encompassing a system's architects' and stakeholders' strategic decisions. A special issue of IEEE Software is intended to raise awareness of architecture sustainability issues and increase interest and work in the area. The

  8. Memory architecture

    NARCIS (Netherlands)

    2012-01-01

    A memory architecture is presented. The memory architecture comprises a first memory and a second memory. The first memory has at least a bank with a first width addressable by a single address. The second memory has a plurality of banks of a second width, said banks being addressable by components

  9. Architectural Narratives

    DEFF Research Database (Denmark)

    Kiib, Hans

    2010-01-01

    a functional framework for these concepts, but tries increasingly to endow the main idea of the cultural project with a spatially aesthetic expression - a shift towards “experience architecture.” A great number of these projects typically recycle and reinterpret narratives related to historical buildings......In this essay, I focus on the combination of programs and the architecture of cultural projects that have emerged within the last few years. These projects are characterized as “hybrid cultural projects,” because they intend to combine experience with entertainment, play, and learning. This essay...... and architectural heritage; another group tries to embed new performative technologies in expressive architectural representation. Finally, this essay provides a theoretical framework for the analysis of the political rationales of these projects and for the architectural representation bridges the gap between...

  10. Chromatin maturation depends on continued DNA-replication

    International Nuclear Information System (INIS)

    Schlaeger, E.J.; Puelm, W.; Knippers, R.

    1983-01-01

    The structure of [ 3 H]thymidine pulse-labeled chromatin in lymphocytes differs from that of non-replicating chromatin by several operational criteria which are related to the higher nuclease sensitivity of replicating chromatin. These structural features of replicating chromatin rapidly disappear when the [ 3 H]thymidine pulse is followed by a chase in the presence of an excess of non-radioactive thymidine. However, when the rate of DNA replication is reduced, as in cycloheximide-treated lymphocytes, chromatin maturation is retarded. No chromatin maturation is observed when nuclei from pulse-labeled lymphocytes are incubated in vitro in the absence of DNA precursors. In contrast, when these nuclei are incubated under conditions known to be optimal for DNA replication, the structure of replicating chromatin is efficiently converted to that of 'mature', non-replicating chromatin. The authors conclude that the properties of nascent DNA and/or the distance from the replication fork are important factors in chromatin maturation. (Auth.)

  11. The Role of Chromatin-Associated Proteins in Cancer

    DEFF Research Database (Denmark)

    Helin, Kristian; Minucci, Saverio

    2017-01-01

    The organization of the chromatin structure is essential for maintaining cell-type-specific gene expression and therefore for cell identity. This structure is highly dynamic and is regulated by a large number of chromatin-associated proteins that are required for normal development...... and differentiation. Recurrent somatic mutations have been found with high frequency in genes coding for chromatin-associated proteins in cancer, and several of these are required for cancer maintenance. In this review, we discuss recent advances in understanding the role of chromatin-associated proteins...

  12. A chromatin insulator driving three-dimensional Polycomb response element (PRE) contacts and Polycomb association with the chromatin fiber

    DEFF Research Database (Denmark)

    Comet, Itys; Schuettengruber, Bernd; Sexton, Tom

    2011-01-01

    to insulate genes from regulatory elements or to take part in long-distance interactions. Using a high-resolution chromatin conformation capture (H3C) method, we show that the Drosophila gypsy insulator behaves as a conformational chromatin border that is able to prohibit contacts between a Polycomb response...... element (PRE) and a distal promoter. On the other hand, two spaced gypsy elements form a chromatin loop that is able to bring an upstream PRE in contact with a downstream gene to mediate its repression. Chromatin immunoprecipitation (ChIP) profiles of the Polycomb protein and its associated H3K27me3...... histone mark reflect this insulator-dependent chromatin conformation, suggesting that Polycomb action at a distance can be organized by local chromatin topology....

  13. Dysregulation of chromatin remodelling complexes in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Tibshirani, Michael; Zhao, Beibei; Gentil, Benoit J; Minotti, Sandra; Marques, Christine; Keith, Julia; Rogaeva, Ekaterina; Zinman, Lorne; Rouaux, Caroline; Robertson, Janice; Durham, Heather D

    2017-11-01

    Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with paralysis resulting from dysfunction and loss of motor neurons. A common neuropathological finding is attrition of motor neuron dendrites, which make central connections vital to motor control. The chromatin remodelling complex, neuronal Brahma-related gene 1 (Brg1)-associated factor complex (nBAF), is critical for neuronal differentiation, dendritic extension and synaptic function. We have identified loss of the crucial nBAF subunits Brg1, Brg1-associated factor 53b and calcium responsive transactivator in cultured motor neurons expressing FUS or TAR-DNA Binding Protein 43 (TDP-43) mutants linked to familial ALS. When plasmids encoding wild-type or mutant human FUS or TDP-43 were expressed in motor neurons of dissociated spinal cord cultures prepared from E13 mice, mutant proteins in particular accumulated in the cytoplasm. Immunolabelling of nBAF subunits was reduced in proportion to loss of nuclear FUS or TDP-43 and depletion of Brg1 was associated with nuclear retention of Brg1 mRNA. Dendritic attrition (loss of intermediate and terminal dendritic branches) occurred in motor neurons expressing mutant, but not wild-type, FUS or TDP-43. This attrition was delayed by ectopic over-expression of Brg1 and was reproduced by inhibiting Brg1 activity either through genetic manipulation or treatment with the chemical inhibitor, (E)-1-(2-Hydroxyphenyl)-3-((1R, 4R)-5-(pyridin-2-yl)-2, 5-diazabicyclo[2.2.1]heptan-2-yl)prop-2-en-1-one, demonstrating the importance of Brg1 to maintenance of dendritic architecture. Loss of nBAF subunits was also documented in spinal motor neurons in autopsy tissue from familial amyotrophic sclerosis (chromosome 9 open reading frame 72 with G4C2 nucleotide expansion) and from sporadic cases with no identified mutation, pointing to dysfunction of nBAF chromatin remodelling in multiple forms of ALS. © The Author 2017. Published by Oxford University Press. All rights reserved

  14. Histone modifications influence mediator interactions with chromatin

    Science.gov (United States)

    Zhu, Xuefeng; Zhang, Yongqiang; Bjornsdottir, Gudrun; Liu, Zhongle; Quan, Amy; Costanzo, Michael; Dávila López, Marcela; Westholm, Jakub Orzechowski; Ronne, Hans; Boone, Charles; Gustafsson, Claes M.; Myers, Lawrence C.

    2011-01-01

    The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. Genome wide localization studies have demonstrated that Mediator occupancy not only correlates with high levels of transcription, but that the complex also is present at transcriptionally silenced locations. We provide evidence that Mediator localization is guided by an interaction with histone tails, and that this interaction is regulated by their post-translational modifications. A quantitative, high-density genetic interaction map revealed links between Mediator components and factors affecting chromatin structure, especially histone deacetylases. Peptide binding assays demonstrated that pure wild-type Mediator forms stable complexes with the tails of Histone H3 and H4. These binding assays also showed Mediator—histone H4 peptide interactions are specifically inhibited by acetylation of the histone H4 lysine 16, a residue critical in transcriptional silencing. Finally, these findings were validated by tiling array analysis that revealed a broad correlation between Mediator and nucleosome occupancy in vivo, but a negative correlation between Mediator and nucleosomes acetylated at histone H4 lysine 16. Our studies show that chromatin structure and the acetylation state of histones are intimately connected to Mediator localization. PMID:21742760

  15. Global chromatin fibre compaction in response to DNA damage

    International Nuclear Information System (INIS)

    Hamilton, Charlotte; Hayward, Richard L.; Gilbert, Nick

    2011-01-01

    Highlights: ► Robust KAP1 phosphorylation in response to DNA damage in HCT116 cells. ► DNA repair foci are found in soluble chromatin. ► Biophysical analysis reveals global chromatin fibre compaction after DNA damage. ► DNA damage is accompanied by rapid linker histone dephosphorylation. -- Abstract: DNA is protected by packaging it into higher order chromatin fibres, but this can impede nuclear processes like DNA repair. Despite considerable research into the factors required for signalling and repairing DNA damage, it is unclear if there are concomitant changes in global chromatin fibre structure. In human cells DNA double strand break (DSB) formation triggers a signalling cascade resulting in H2AX phosphorylation (γH2AX), the rapid recruitment of chromatin associated proteins and the subsequent repair of damaged sites. KAP1 is a transcriptional corepressor and in HCT116 cells we found that after DSB formation by chemicals or ionising radiation there was a wave of, predominantly ATM dependent, KAP1 phosphorylation. Both KAP1 and phosphorylated KAP1 were readily extracted from cells indicating they do not have a structural role and γH2AX was extracted in soluble chromatin indicating that sites of damage are not attached to an underlying structural matrix. After DSB formation we did not find a concomitant change in the sensitivity of chromatin fibres to micrococcal nuclease digestion. Therefore to directly investigate higher order chromatin fibre structures we used a biophysical sedimentation technique based on sucrose gradient centrifugation to compare the conformation of chromatin fibres isolated from cells before and after DNA DSB formation. After damage we found global chromatin fibre compaction, accompanied by rapid linker histone dephosphorylation, consistent with fibres being more regularly folded or fibre deformation being stabilized by linker histones. We suggest that following DSB formation, although there is localised chromatin unfolding to

  16. Architectural technology

    DEFF Research Database (Denmark)

    2005-01-01

    The booklet offers an overall introduction to the Institute of Architectural Technology and its projects and activities, and an invitation to the reader to contact the institute or the individual researcher for further information. The research, which takes place at the Institute of Architectural...... Technology at the Roayl Danish Academy of Fine Arts, School of Architecture, reflects a spread between strategic, goal-oriented pilot projects, commissioned by a ministry, a fund or a private company, and on the other hand projects which originate from strong personal interests and enthusiasm of individual...

  17. Systemic Architecture

    DEFF Research Database (Denmark)

    Poletto, Marco; Pasquero, Claudia

    -up or tactical design, behavioural space and the boundary of the natural and the artificial realms within the city and architecture. A new kind of "real-time world-city" is illustrated in the form of an operational design manual for the assemblage of proto-architectures, the incubation of proto-gardens...... and the coding of proto-interfaces. These prototypes of machinic architecture materialize as synthetic hybrids embedded with biological life (proto-gardens), computational power, behavioural responsiveness (cyber-gardens), spatial articulation (coMachines and fibrous structures), remote sensing (FUNclouds...

  18. Humanizing Architecture

    DEFF Research Database (Denmark)

    Toft, Tanya Søndergaard

    2015-01-01

    The article proposes the urban digital gallery as an opportunity to explore the relationship between ‘human’ and ‘technology,’ through the programming of media architecture. It takes a curatorial perspective when proposing an ontological shift from considering media facades as visual spectacles...... agency and a sense of being by way of dematerializing architecture. This is achieved by way of programming the symbolic to provide new emotional realizations and situations of enlightenment in the public audience. This reflects a greater potential to humanize the digital in media architecture....

  19. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen

    environments and a knowledge gap therefore exists in present hospital designs. Consequently, the purpose of this thesis has been to investigate if any research-based knowledge exist supporting the hypothesis that the interior architectural qualities of eating environments influence patient food intake, health...... and well-being, as well as outline a set of basic design principles ‘predicting’ the future interior architectural qualities of patient eating environments. Methodologically the thesis is based on an explorative study employing an abductive approach and hermeneutic-interpretative strategy utilizing tactics...... and food intake, as well as a series of references exist linking the interior architectural qualities of healthcare environments with the health and wellbeing of patients. On the basis of these findings, the thesis presents the concept of Architectural Theatricality as well as a set of design principles...

  20. Homoeologous chromatin exchange in a radiation-induced gene transfer

    International Nuclear Information System (INIS)

    Dvorak, J.; Knott, D.R.

    1977-01-01

    Some of the ionizing-radiation-induced translocations between alien and wheat chromosomes show no deleterious effects and are transmitted normally through the pollen. Translocations of this type will be called ''compensating''. In one such compensating translocation, designated T4, it was found that chromatin in the long arm of wheat chromosome 7D was replaced with homoeologous chromatin of the Agropyron chromosome

  1. Chromatin Immunoprecipitation (ChIP) using Drosophila tissue

    OpenAIRE

    Tran, Vuong; Gan, Qiang; Chen, Xin

    2012-01-01

    Epigenetics remains a rapidly developing field that studies how the chromatin state contributes to differential gene expression in distinct cell types at different developmental stages. Epigenetic regulation contributes to a broad spectrum of biological processes, including cellular differentiation during embryonic development and homeostasis in adulthood. A critical strategy in epigenetic studies is to examine how various histone modifications and chromatin factors regulate gene expression. ...

  2. Homoeologous chromatin exchange in a radiation-induced gene transfer

    Energy Technology Data Exchange (ETDEWEB)

    Dvorak, J; Knott, D R [Department of Crop Science, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    1977-03-01

    Some of the ionizing-radiation-induced translocations between alien and wheat chromosomes show no deleterious effects and are transmitted normally through the pollen. Translocations of this type will be called ''compensating''. In one such compensating translocation, designated T4, it was found that chromatin in the long arm of wheat chromosome 7D was replaced with homologous chromatin of the Agropyron chromosome.

  3. The nucleosome: orchestrating DNA damage signaling and repair within chromatin.

    Science.gov (United States)

    Agarwal, Poonam; Miller, Kyle M

    2016-10-01

    DNA damage occurs within the chromatin environment, which ultimately participates in regulating DNA damage response (DDR) pathways and repair of the lesion. DNA damage activates a cascade of signaling events that extensively modulates chromatin structure and organization to coordinate DDR factor recruitment to the break and repair, whilst also promoting the maintenance of normal chromatin functions within the damaged region. For example, DDR pathways must avoid conflicts between other DNA-based processes that function within the context of chromatin, including transcription and replication. The molecular mechanisms governing the recognition, target specificity, and recruitment of DDR factors and enzymes to the fundamental repeating unit of chromatin, i.e., the nucleosome, are poorly understood. Here we present our current view of how chromatin recognition by DDR factors is achieved at the level of the nucleosome. Emerging evidence suggests that the nucleosome surface, including the nucleosome acidic patch, promotes the binding and activity of several DNA damage factors on chromatin. Thus, in addition to interactions with damaged DNA and histone modifications, nucleosome recognition by DDR factors plays a key role in orchestrating the requisite chromatin response to maintain both genome and epigenome integrity.

  4. Nuclear visions enhanced: chromatin structure, organization and dynamics

    OpenAIRE

    Meshorer, Eran; Herrmann, Harald; Raška, Ivan

    2011-01-01

    The EMBO Workshop on ‘Chromatin Structure, Organization and Dynamics' took place in April 2011 in Prague, Czech Republic. Participants presented data on the generation of models of the genome, working to correlate changes in the organization of chromatin with the functional state of the genome.

  5. HAMLET interacts with histones and chromatin in tumor cell nuclei.

    Science.gov (United States)

    Düringer, Caroline; Hamiche, Ali; Gustafsson, Lotta; Kimura, Hiroshi; Svanborg, Catharina

    2003-10-24

    HAMLET is a folding variant of human alpha-lactalbumin in an active complex with oleic acid. HAMLET selectively enters tumor cells, accumulates in their nuclei and induces apoptosis-like cell death. This study examined the interactions of HAMLET with nuclear constituents and identified histones as targets. HAMLET was found to bind histone H3 strongly and to lesser extent histones H4 and H2B. The specificity of these interactions was confirmed using BIAcore technology and chromatin assembly assays. In vivo in tumor cells, HAMLET co-localized with histones and perturbed the chromatin structure; HAMLET was found associated with chromatin in an insoluble nuclear fraction resistant to salt extraction. In vitro, HAMLET bound strongly to histones and impaired their deposition on DNA. We conclude that HAMLET interacts with histones and chromatin in tumor cell nuclei and propose that this interaction locks the cells into the death pathway by irreversibly disrupting chromatin organization.

  6. The AID-induced DNA damage response in chromatin

    DEFF Research Database (Denmark)

    Daniel, Jeremy A; Nussenzweig, André

    2013-01-01

    Chemical modifications to the DNA and histone protein components of chromatin can modulate gene expression and genome stability. Understanding the physiological impact of changes in chromatin structure remains an important question in biology. As one example, in order to generate antibody diversity...... with somatic hypermutation and class switch recombination, chromatin must be made accessible for activation-induced cytidine deaminase (AID)-mediated deamination of cytosines in DNA. These lesions are recognized and removed by various DNA repair pathways but, if not handled properly, can lead to formation...... of oncogenic chromosomal translocations. In this review, we focus the discussion on how chromatin-modifying activities and -binding proteins contribute to the native chromatin environment in which AID-induced DNA damage is targeted and repaired. Outstanding questions remain regarding the direct roles...

  7. Fast neutron irradiation effects on liver chromatin structure

    International Nuclear Information System (INIS)

    Constantinescu, B.; Radu, L.

    1996-01-01

    The growing interest in neutron therapy requires complex studies on the mechanisms of neutron action on biological systems, especially on chromatin. The chromatin was extracted from a normal tissue-livers of Wistar rats - and from a tumoral tissue - Walker tumour maintained on Wistar rats. Irradiation doses from 5 Gy to 100 Gy by fast neutron intense beams produced via d(13.5 MeV) +Be (thick target) reaction at Bucharest U-120 Classical Cyclotron were used. To study the post-irradiation effects, various methods were employed. So, the variation in the 260 nm absorbency in chromatin thermal transition was pursuit. The chromatin-ethidium bromide complexes fluorescence with λ ex =480 nm and λ em =600 nm was analyzed. To determine chromatin DNA strand breaks a fluorimetric method, with cells' suspensions as starting material was used. This method requires a partial treatment with alkali producing three components: T-estimating the total fluorescence of DNA double helix, P-assigning the untwisting rate and B-the blank, where DNA is completely unfolded The percentsge of DNA double strand,-D-, remaining after this treatment, is: %D=100x(P-B)/(T-B). The intrinsic chromatin fluorescence was determined for tyrosine (λ ex =280 nm, λ em =305 nm), specific for badic chromatin prooteins, and for tryptophane (λ ex =290 nm, λ em =345 nm) specific for acid chromatin proteins. Polyacrylamide gel electrophoresis was performed: The double fluorescent labelling of chromatin was realized with acridine orange for DNA and with dansyl chloride for chromatin proteins. Fluorescence intensity determinations were done with λ ex =505 nm, λ em =530 nm for acridine orange and with λ ex =323 nm, λ em =505 nm for dansyl chloride. A Pye Unicam SP 1800 spectrophotometer and a Aminco SPF 500 spectrofluorimeter were employed. (author)

  8. Architectural freedom and industrialized architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...... proportions, to organize the process on site choosing either one room wall components or several rooms wall components – either horizontally or vertically. Combined with the seamless joint the playing with these possibilities the new industrialized architecture can deliver variations in choice of solutions...... for retrofit design. If we add the question of the installations e.g. ventilation to this systematic thinking of building technique we get a diverse and functional architecture, thereby creating a new and clearer story telling about new and smart system based thinking behind architectural expression....

  9. Architectural freedom and industrialized architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    to explain that architecture can be thought as a complex and diverse design through customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performing expression in direct relation to the given context. Through the last couple of years we have...... expression in the specific housing area. It is the aim of this article to expand the different design strategies which architects can use – to give the individual project attitudes and designs with architectural quality. Through the customized component production it is possible to choose different...... for retrofit design. If we add the question of the installations e.g. ventilation to this systematic thinking of building technique we get a diverse and functional architecture, thereby creating a new and clearer story telling about new and smart system based thinking behind architectural expression....

  10. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    Architectural freedom and industrialized architecture. Inge Vestergaard, Associate Professor, Cand. Arch. Aarhus School of Architecture, Denmark Noerreport 20, 8000 Aarhus C Telephone +45 89 36 0000 E-mai l inge.vestergaard@aarch.dk Based on the repetitive architecture from the "building boom" 1960...... customization, telling exactly the revitalized storey about the change to a contemporary sustainable and better performed expression in direct relation to the given context. Through the last couple of years we have in Denmark been focusing a more sustainable and low energy building technique, which also include...... to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...

  11. PICNIC Architecture.

    Science.gov (United States)

    Saranummi, Niilo

    2005-01-01

    The PICNIC architecture aims at supporting inter-enterprise integration and the facilitation of collaboration between healthcare organisations. The concept of a Regional Health Economy (RHE) is introduced to illustrate the varying nature of inter-enterprise collaboration between healthcare organisations collaborating in providing health services to citizens and patients in a regional setting. The PICNIC architecture comprises a number of PICNIC IT Services, the interfaces between them and presents a way to assemble these into a functioning Regional Health Care Network meeting the needs and concerns of its stakeholders. The PICNIC architecture is presented through a number of views relevant to different stakeholder groups. The stakeholders of the first view are national and regional health authorities and policy makers. The view describes how the architecture enables the implementation of national and regional health policies, strategies and organisational structures. The stakeholders of the second view, the service viewpoint, are the care providers, health professionals, patients and citizens. The view describes how the architecture supports and enables regional care delivery and process management including continuity of care (shared care) and citizen-centred health services. The stakeholders of the third view, the engineering view, are those that design, build and implement the RHCN. The view comprises four sub views: software engineering, IT services engineering, security and data. The proposed architecture is founded into the main stream of how distributed computing environments are evolving. The architecture is realised using the web services approach. A number of well established technology platforms and generic standards exist that can be used to implement the software components. The software components that are specified in PICNIC are implemented in Open Source.

  12. Architectural freedom and industrialised architecture

    DEFF Research Database (Denmark)

    Vestergaard, Inge

    2012-01-01

    to the building physic problems a new industrialized period has started based on light weight elements basically made of wooden structures, faced with different suitable materials meant for individual expression for the specific housing area. It is the purpose of this article to widen up the different design...... to this systematic thinking of the building technique we get a diverse and functional architecture. Creating a new and clearer story telling about new and smart system based thinking behind the architectural expression....

  13. RNA polymerase III transcription - regulated by chromatin structure and regulator of nuclear chromatin organization.

    Science.gov (United States)

    Pascali, Chiara; Teichmann, Martin

    2013-01-01

    RNA polymerase III (Pol III) transcription is regulated by modifications of the chromatin. DNA methylation and post-translational modifications of histones, such as acetylation, phosphorylation and methylation have been linked to Pol III transcriptional activity. In addition to being regulated by modifications of DNA and histones, Pol III genes and its transcription factors have been implicated in the organization of nuclear chromatin in several organisms. In yeast, the ability of the Pol III transcription system to contribute to nuclear organization seems to be dependent on direct interactions of Pol III genes and/or its transcription factors TFIIIC and TFIIIB with the structural maintenance of chromatin (SMC) protein-containing complexes cohesin and condensin. In human cells, Pol III genes and transcription factors have also been shown to colocalize with cohesin and the transcription regulator and genome organizer CCCTC-binding factor (CTCF). Furthermore, chromosomal sites have been identified in yeast and humans that are bound by partial Pol III machineries (extra TFIIIC sites - ETC; chromosome organizing clamps - COC). These ETCs/COC as well as Pol III genes possess the ability to act as boundary elements that restrict spreading of heterochromatin.

  14. Architectural geometry

    KAUST Repository

    Pottmann, Helmut; Eigensatz, Michael; Vaxman, Amir; Wallner, Johannes

    2014-01-01

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

  15. Architectural geometry

    KAUST Repository

    Pottmann, Helmut

    2014-11-26

    Around 2005 it became apparent in the geometry processing community that freeform architecture contains many problems of a geometric nature to be solved, and many opportunities for optimization which however require geometric understanding. This area of research, which has been called architectural geometry, meanwhile contains a great wealth of individual contributions which are relevant in various fields. For mathematicians, the relation to discrete differential geometry is significant, in particular the integrable system viewpoint. Besides, new application contexts have become available for quite some old-established concepts. Regarding graphics and geometry processing, architectural geometry yields interesting new questions but also new objects, e.g. replacing meshes by other combinatorial arrangements. Numerical optimization plays a major role but in itself would be powerless without geometric understanding. Summing up, architectural geometry has become a rewarding field of study. We here survey the main directions which have been pursued, we show real projects where geometric considerations have played a role, and we outline open problems which we think are significant for the future development of both theory and practice of architectural geometry.

  16. Relational Architecture

    DEFF Research Database (Denmark)

    Reeh, Henrik

    2018-01-01

    in a scholarly institution (element #3), as well as the certified PhD scholar (element #4) and the architectural profession, notably its labour market (element #5). This first layer outlines the contemporary context which allows architectural research to take place in a dynamic relationship to doctoral education...... a human and institutional development going on since around 1990 when the present PhD institution was first implemented in Denmark. To be sure, the model is centred around the PhD dissertation (element #1). But it involves four more components: the PhD candidate (element #2), his or her supervisor...... and interrelated fields in which history, place, and sound come to emphasize architecture’s relational qualities rather than the apparent three-dimensional solidity of constructed space. A third layer of relational architecture is at stake in the professional experiences after the defence of the authors...

  17. Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    Architecture and anthropology have always had a common focus on dwelling, housing, urban life and spatial organisation. Current developments in both disciplines make it even more relevant to explore their boundaries and overlaps. Architects are inspired by anthropological insights and methods......, while recent material and spatial turns in anthropology have also brought an increasing interest in design, architecture and the built environment. Understanding the relationship between the social and the physical is at the heart of both disciplines, and they can obviously benefit from further...... collaboration: How can qualitative anthropological approaches contribute to contemporary architecture? And just as importantly: What can anthropologists learn from architects’ understanding of spatial and material surroundings? Recent theoretical developments in anthropology stress the role of materials...

  18. Architectural Engineers

    DEFF Research Database (Denmark)

    Petersen, Rikke Premer

    engineering is addresses from two perspectives – as an educational response and an occupational constellation. Architecture and engineering are two of the traditional design professions and they frequently meet in the occupational setting, but at educational institutions they remain largely estranged....... The paper builds on a multi-sited study of an architectural engineering program at the Technical University of Denmark and an architectural engineering team within an international engineering consultancy based on Denmark. They are both responding to new tendencies within the building industry where...... the role of engineers and architects increasingly overlap during the design process, but their approaches reflect different perceptions of the consequences. The paper discusses some of the challenges that design education, not only within engineering, is facing today: young designers must be equipped...

  19. Rapid and reversible epigenome editing by endogenous chromatin regulators.

    Science.gov (United States)

    Braun, Simon M G; Kirkland, Jacob G; Chory, Emma J; Husmann, Dylan; Calarco, Joseph P; Crabtree, Gerald R

    2017-09-15

    Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells. Furthermore, Hp1/Suv39h1 heterochromatin complex recruitment to active promoters deposits H3K9me3 domains, resulting in gene silencing that can be reversed upon washout of the chemical dimerizer. This inducible recruitment strategy provides precise kinetic information to model epigenetic memory and plasticity. It is broadly applicable to mechanistic studies of chromatin in mammalian cells and is particularly suited to the analysis of endogenous multi-subunit chromatin regulator complexes.Understanding the link between epigenetic marks and gene regulation requires the development of new tools to directly manipulate chromatin. Here the authors demonstrate a Cas9-based system to recruit chromatin remodelers to loci of interest, allowing rapid, reversible manipulation of epigenetic states.

  20. Chromatinization of the KSHV Genome During the KSHV Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    Uppal, Timsy [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Jha, Hem C. [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States); Verma, Subhash C. [Department of Microbiology and Immunology, School of Medicine, University of Nevada, 1664 N Virginia Street, MS 320, Reno, NV 89557 (United States); Robertson, Erle S., E-mail: erle@mail.med.upenn.edu [Department of Microbiology and the Tumor Virology Program of the Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, 201E Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104 (United States)

    2015-01-14

    Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle.

  1. Chromatinization of the KSHV Genome During the KSHV Life Cycle

    International Nuclear Information System (INIS)

    Uppal, Timsy; Jha, Hem C.; Verma, Subhash C.; Robertson, Erle S.

    2015-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV) belongs to the gamma herpesvirus family and is the causative agent of various lymphoproliferative diseases in humans. KSHV, like other herpesviruses, establishes life-long latent infection with the expression of a limited number of viral genes. Expression of these genes is tightly regulated by both the viral and cellular factors. Recent advancements in identifying the expression profiles of viral transcripts, using tilling arrays and next generation sequencing have identified additional coding and non-coding transcripts in the KSHV genome. Determining the functions of these transcripts will provide a better understanding of the mechanisms utilized by KSHV in altering cellular pathways involved in promoting cell growth and tumorigenesis. Replication of the viral genome is critical in maintaining the existing copies of the viral episomes during both latent and lytic phases of the viral life cycle. The replication of the viral episome is facilitated by viral components responsible for recruiting chromatin modifying enzymes and replication factors for altering the chromatin complexity and replication initiation functions, respectively. Importantly, chromatin modification of the viral genome plays a crucial role in determining whether the viral genome will persist as latent episome or undergo lytic reactivation. Additionally, chromatinization of the incoming virion DNA, which lacks chromatin structure, in the target cells during primary infection, helps in establishing latent infection. Here, we discuss the recent advancements on our understating of KSHV genome chromatinization and the consequences of chromatin modifications on viral life cycle

  2. Chromatin decondensed by acetylation shows an elevated radiation response

    International Nuclear Information System (INIS)

    Nackerdien, Z.; Michie, J.; Boehm, L.

    1989-01-01

    V-79 Chinese hamster lung fibroblasts exposed to 5 mM n-sodium butyrate were irradiated with 60Co gamma rays and cell survival was determined by the cell colony assay. In a separate set of experiments the acetylated chromatin obtained from these cells was irradiated and the change of molecular weight of the DNA was evaluated by alkaline sucrose density centrifugation. At a survival level of 10(-2) to 10(-4) cells exposed to butyrate were found to be 1.3-1.4 times more radiosensitive than control cells. Exposure of isolated chromatin to 100 Gy of 60Co gamma irradiation generated 0.9 +/- 0.03 single-strand breaks (ssb) per 10 Gy per 10(8) Da and 2.0 +/- 0.3 ssb/10 Gy/10(8) Da for control and acetylated chromatin, respectively. The elevated radiation sensitivity of chromatin relaxed by acetylation is in good agreement with previous results on chromatin expanded by histone H1 depletion. Packing and accessibility of DNA in chromatin appear to be major factors which influence the radiation sensitivity. The intrinsic radiation sensitivity of chromatin in various packing states is discussed in light of the variation of radiation sensitivity of whole cells in the cell cycle which incorporates repair

  3. PREDICTION OF CHROMATIN STATES USING DNA SEQUENCE PROPERTIES

    KAUST Repository

    Bahabri, Rihab R.

    2013-06-01

    Activities of DNA are to a great extent controlled epigenetically through the internal struc- ture of chromatin. This structure is dynamic and is influenced by different modifications of histone proteins. Various combinations of epigenetic modification of histones pinpoint to different functional regions of the DNA determining the so-called chromatin states. How- ever, the characterization of chromatin states by the DNA sequence properties remains largely unknown. In this study we aim to explore whether DNA sequence patterns in the human genome can characterize different chromatin states. Using DNA sequence motifs we built binary classifiers for each chromatic state to eval- uate whether a given genomic sequence is a good candidate for belonging to a particular chromatin state. Of four classification algorithms (C4.5, Naive Bayes, Random Forest, and SVM) used for this purpose, the decision tree based classifiers (C4.5 and Random Forest) yielded best results among those we evaluated. Our results suggest that in general these models lack sufficient predictive power, although for four chromatin states (insulators, het- erochromatin, and two types of copy number variation) we found that presence of certain motifs in DNA sequences does imply an increased probability that such a sequence is one of these chromatin states.

  4. Tracking the mechanical dynamics of human embryonic stem cell chromatin

    Directory of Open Access Journals (Sweden)

    Hinde Elizabeth

    2012-12-01

    Full Text Available Abstract Background A plastic chromatin structure has emerged as fundamental to the self-renewal and pluripotent capacity of embryonic stem (ES cells. Direct measurement of chromatin dynamics in vivo is, however, challenging as high spatiotemporal resolution is required. Here, we present a new tracking-based method which can detect high frequency chromatin movement and quantify the mechanical dynamics of chromatin in live cells. Results We use this method to study how the mechanical properties of chromatin movement in human embryonic stem cells (hESCs are modulated spatiotemporally during differentiation into cardiomyocytes (CM. Notably, we find that pluripotency is associated with a highly discrete, energy-dependent frequency of chromatin movement that we refer to as a ‘breathing’ state. We find that this ‘breathing’ state is strictly dependent on the metabolic state of the cell and is progressively silenced during differentiation. Conclusions We thus propose that the measured chromatin high frequency movements in hESCs may represent a hallmark of pluripotency and serve as a mechanism to maintain the genome in a transcriptionally accessible state. This is a result that could not have been observed without the high spatial and temporal resolution provided by this novel tracking method.

  5. Anti-chromatin antibodies in juvenile rheumatoid arthritis

    Directory of Open Access Journals (Sweden)

    V. Gerloni

    2011-09-01

    Full Text Available Objective: to evaluate the prevalence and clinical significance of anti-chromatin antibodies (Abs in juvenile rheumatoid arthritis (JRA. Methods: IgG anti-chromatin Abs were detected by an enzyme-linked immunosorbent assay (ELISA, in sera of 94 children with JRA (10 children with systemic, 38 with polyarticular and 46 with oligoarticular disease onset. As control group, 33 age- and-sex-matched healthy children (HC were also examined. Results: Abs to chromatin were detected in 24/94 (25,5% of children suffering from JRA. Particularly, the higher prevalence of anti-chromatin Abs has been found in children with oligoarticular (30,4% and polyarticular (23,7% onset JRA. In these groups Abs titers were significantly higher compared to systemic JRA and HC (p=0.003. Anti-chromatin Abs were observed more frequently in patients with oligoarticular disease and chronic uveitis (21,7%. Furthermore, higher levels of anti-chromatin Abs has been found in all the patients treated with anti-TNFα therapy (p<0.0001. Conclusions: our results confirm previous data about the prevalence of anti-chromatin Abs in JRA. These Abs were significantly higher in the group of patients with oligoarticular onset with past or present hystory of ocular involvement and in the group with polyarticular JRA treated with biologic therapy. A long-term follow-up study could be useful to evaluate the potential utility of these autoantibodies.

  6. Intracellular manipulation of chromatin using magnetic nanoparticles

    NARCIS (Netherlands)

    Kanger, Johannes S.; Subramaniam, Vinod; van Driel, Roel

    2008-01-01

    Magnetic tweezers are widely used for manipulating small magnetic beads inside the cell cytoplasm in order to gain insight into the structural and mechanical properties of the cytoskeleton. Here we discuss the use of magnetic tweezers for the study of nuclear architecture and the mechanical

  7. Analysis of DNA replication associated chromatin decondensation: in vivo assay for understanding chromatin remodeling mechanisms of selected proteins.

    Science.gov (United States)

    Borysov, Sergiy; Bryant, Victoria L; Alexandrow, Mark G

    2015-01-01

    Of critical importance to many of the events underlying transcriptional control of gene expression are modifications to core and linker histones that regulate the accessibility of trans-acting factors to the DNA substrate within the context of chromatin. Likewise, control over the initiation of DNA replication, as well as the ability of the replication machinery to proceed during elongation through the multiple levels of chromatin condensation that are likely to be encountered, is known to involve the creation of chromatin accessibility. In the latter case, chromatin access will likely need to be a transient event so as to prevent total genomic unraveling of the chromatin that would be deleterious to cells. While there are many molecular and biochemical approaches in use to study histone changes and their relationship to transcription and chromatin accessibility, few techniques exist that allow a molecular dissection of the events underlying DNA replication control as it pertains to chromatin changes and accessibility. Here, we outline a novel experimental strategy for addressing the ability of specific proteins to induce large-scale chromatin unfolding (decondensation) in vivo upon site-specific targeting to an engineered locus. Our laboratory has used this powerful system in novel ways to directly address the ability of DNA replication proteins to create chromatin accessibility, and have incorporated modifications to the basic approach that allow for a molecular genetic analysis of the mechanisms and associated factors involved in causing chromatin decondensation by a protein of interest. Alternative approaches involving co-expression of other proteins (competitors or stimulators), concurrent drug treatments, and analysis of co-localizing histone modifications are also addressed, all of which are illustrative of the utility of this experimental system for extending basic findings to physiologically relevant mechanisms. Although used by our group to analyze

  8. Reframing Architecture

    DEFF Research Database (Denmark)

    Riis, Søren

    2013-01-01

    I would like to thank Prof. Stephen Read (2011) and Prof. Andrew Benjamin (2011) for both giving inspiring and elaborate comments on my article “Dwelling in-between walls: the architectural surround”. As I will try to demonstrate below, their two different responses not only supplement my article...... focuses on how the absence of an initial distinction might threaten the endeavour of my paper. In my reply to Read and Benjamin, I will discuss their suggestions and arguments, while at the same time hopefully clarifying the postphenomenological approach to architecture....

  9. Chromatin regulation at the frontier of synthetic biology

    Science.gov (United States)

    Keung, Albert J.; Joung, J. Keith; Khalil, Ahmad S.; Collins, James J.

    2016-01-01

    As synthetic biology approaches are extended to diverse applications throughout medicine, biotechnology and basic biological research, there is an increasing need to engineer yeast, plant and mammalian cells. Eukaryotic genomes are regulated by the diverse biochemical and biophysical states of chromatin, which brings distinct challenges, as well as opportunities, over applications in bacteria. Recent synthetic approaches, including `epigenome editing', have allowed the direct and functional dissection of many aspects of physiological chromatin regulation. These studies lay the foundation for biomedical and biotechnological engineering applications that could take advantage of the unique combinatorial and spatiotemporal layers of chromatin regulation to create synthetic systems of unprecedented sophistication. PMID:25668787

  10. SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage

    DEFF Research Database (Denmark)

    Hendriks, Ivo A; Treffers, Louise W; Verlaan-de Vries, Matty

    2015-01-01

    dynamically SUMOylated interaction networks of chromatin modifiers, transcription factors, DNA repair factors, and nuclear body components. SUMOylated chromatin modifiers include JARID1B/KDM5B, JARID1C/KDM5C, p300, CBP, PARP1, SetDB1, and MBD1. Whereas SUMOylated JARID1B was ubiquitylated by the SUMO......-targeted ubiquitin ligase RNF4 and degraded by the proteasome in response to DNA damage, JARID1C was SUMOylated and recruited to the chromatin to demethylate histone H3K4....

  11. DNA packing in chromatine, a manifestation of the Bonnet transformation.

    Science.gov (United States)

    Blum, Z; Lidin, S

    1988-08-01

    The packing of DNA is described using the formalism of differential geometry. Winding of the DNA double helix around the histone 2-5 octamer forming a nucleosome and the condensation of the so-formed bead-on-a-string chromatine aided by histone 1 is interpreted as two consecutive isometric, i.e. Bonnet, transformations. The DNA double helix can be approximated to a helicoid which can be transformed isometrically to a catenoid, an approximation of the nucleosome. Owing to the organization of the histone octamer the extended chromatine takes a helicoidal shape allowing a second Bonnet transformation to consummate the condensation into a chromatine fibre.

  12. Mechanism of chromatin degradation in thymocytes of irradiated rats

    International Nuclear Information System (INIS)

    Zotova, R.N.; Umanskij, S.R.; Tokarskaya, V.I.

    1983-01-01

    A biphase change in poly (ADP-ribose) polymerase activity of the thymocyte chromatin was observed after 10 Gy irradiation of rats: during the first minutes the incorporation of 14 C-NAD increased by 40% then started decreasing to make 110, 60 and 35% after 1, 2 and 3 h, respectively. Irradiation of rat thymus chromatin in vitro sharply decreased poly (ADP-ribose) polymerase activity. The possible role of changes in the poly (ADP-ribose) synthesis in the activation of nuclear Ca/Mg-dependent endonuclease and in the postirradiation degradation of the thymocyte chromatin is discussed

  13. Initial high-resolution microscopic mapping of active and inactive regulatory sequences proves non-random 3D arrangements in chromatin domain clusters.

    Science.gov (United States)

    Cremer, Marion; Schmid, Volker J; Kraus, Felix; Markaki, Yolanda; Hellmann, Ines; Maiser, Andreas; Leonhardt, Heinrich; John, Sam; Stamatoyannopoulos, John; Cremer, Thomas

    2017-08-07

    The association of active transcription regulatory elements (TREs) with DNAse I hypersensitivity (DHS[+]) and an 'open' local chromatin configuration has long been known. However, the 3D topography of TREs within the nuclear landscape of individual cells in relation to their active or inactive status has remained elusive. Here, we explored the 3D nuclear topography of active and inactive TREs in the context of a recently proposed model for a functionally defined nuclear architecture, where an active and an inactive nuclear compartment (ANC-INC) form two spatially co-aligned and functionally interacting networks. Using 3D structured illumination microscopy, we performed 3D FISH with differently labeled DNA probe sets targeting either sites with DHS[+], apparently active TREs, or DHS[-] sites harboring inactive TREs. Using an in-house image analysis tool, DNA targets were quantitatively mapped on chromatin compaction shaped 3D nuclear landscapes. Our analyses present evidence for a radial 3D organization of chromatin domain clusters (CDCs) with layers of increasing chromatin compaction from the periphery to the CDC core. Segments harboring active TREs are significantly enriched at the decondensed periphery of CDCs with loops penetrating into interchromatin compartment channels, constituting the ANC. In contrast, segments lacking active TREs (DHS[-]) are enriched toward the compacted interior of CDCs (INC). Our results add further evidence in support of the ANC-INC network model. The different 3D topographies of DHS[+] and DHS[-] sites suggest positional changes of TREs between the ANC and INC depending on their functional state, which might provide additional protection against an inappropriate activation. Our finding of a structural organization of CDCs based on radially arranged layers of different chromatin compaction levels indicates a complex higher-order chromatin organization beyond a dichotomic classification of chromatin into an 'open,' active and 'closed

  14. Textile Architecture

    DEFF Research Database (Denmark)

    Heimdal, Elisabeth Jacobsen

    2010-01-01

    Textiles can be used as building skins, adding new aesthetic and functional qualities to architecture. Just like we as humans can put on a coat, buildings can also get dressed. Depending on our mood, or on the weather, we can change coat, and so can the building. But the idea of using textiles...

  15. Insights into Chromatin Structure and Dynamics in Plants

    Directory of Open Access Journals (Sweden)

    Stefanie Rosa

    2013-11-01

    Full Text Available The packaging of chromatin into the nucleus of a eukaryotic cell requires an extraordinary degree of compaction and physical organization. In recent years, it has been shown that this organization is dynamically orchestrated to regulate responses to exogenous stimuli as well as to guide complex cell-type-specific developmental programs. Gene expression is regulated by the compartmentalization of functional domains within the nucleus, by distinct nucleosome compositions accomplished via differential modifications on the histone tails and through the replacement of core histones by histone variants. In this review, we focus on these aspects of chromatin organization and discuss novel approaches such as live cell imaging and photobleaching as important tools likely to give significant insights into our understanding of the very dynamic nature of chromatin and chromatin regulatory processes. We highlight the contribution plant studies have made in this area showing the potential advantages of plants as models in understanding this fundamental aspect of biology.

  16. Probing Chromatin-modifying Enzymes with Chemical Tools

    KAUST Repository

    Fischle, Wolfgang

    2016-02-04

    Chromatin is the universal template of genetic information in all eukaryotic organisms. Chemical modifications of the DNA-packaging histone proteins and the DNA bases are crucial signaling events in directing the use and readout of eukaryotic genomes. The enzymes that install and remove these chromatin modifications as well as the proteins that bind these marks govern information that goes beyond the sequence of DNA. Therefore, these so-called epigenetic regulators are intensively studied and represent promising drug targets in modern medicine. We summarize and discuss recent advances in the field of chemical biology that have provided chromatin research with sophisticated tools for investigating the composition, activity, and target sites of chromatin modifying enzymes and reader proteins.

  17. HACking the centromere chromatin code: insights from human artificial chromosomes.

    Science.gov (United States)

    Bergmann, Jan H; Martins, Nuno M C; Larionov, Vladimir; Masumoto, Hiroshi; Earnshaw, William C

    2012-07-01

    The centromere is a specialized chromosomal region that serves as the assembly site of the kinetochore. At the centromere, CENP-A nucleosomes form part of a chromatin landscape termed centrochromatin. This chromatin environment conveys epigenetic marks regulating kinetochore formation. Recent work sheds light on the intricate relationship between centrochromatin state, the CENP-A assembly pathway and the maintenance of centromere function. Here, we review the emerging picture of how chromatin affects mammalian kinetochore formation. We place particular emphasis on data obtained from Human Artificial Chromosome (HAC) biology and the targeted engineering of centrochromatin using synthetic HACs. We discuss implications of these findings, which indicate that a delicate balance of histone modifications and chromatin state dictates both de novo centromere formation and the maintenance of centromere identity in dividing cell populations.

  18. histone H3 predominantly mark the pericentromeric chromatin

    Indian Academy of Sciences (India)

    SANTOSH KUMAR SHARMA

    pericentromeric chromatin during mitosis in monokinetic plants. J. Genet. .... bigger), cytological preparations (easy to difficult) as well as their habitat ... Poaceae. Monocot. Land. 14. Triticum aestivum. Common wheat. Poaceae. Monocot. Land.

  19. Neutron scattering studies on chromatin higher-order structure

    Energy Technology Data Exchange (ETDEWEB)

    Graziano, V.; Gerchman, S.E.; Schneider, D.K.; Ramakrishnan, V. [Brookhaven National Laboratory, Upton, NY (United States)

    1994-12-31

    We have been engaged in studies of the structure and condensation of chromatin into the 30nm filament using small-angle neutron scattering. We have also used deuterated histone H1 to determine its location in the chromatin 30nm filament. Our studies indicate that chromatin condenses with increasing ionic strength to a limiting structure that has a mass per unit length of 6-7 nucleosomes/11 nm. They also show that the linker histone H1/H5 is located in the interior of the chromatin filament, in a position compatible with its binding to the inner face of the nucleosome. Analysis of the mass per unit length as a function of H5 stoichiometry suggests that 5-7 contiguous nucleosomes need to have H5 bound before a stable higher order structure can exist.

  20. Shelterin Protects Chromosome Ends by Compacting Telomeric Chromatin

    Science.gov (United States)

    Bandaria, Jigar N.; Qin, Peiwu; Berk, Veysel; Chu, Steven; Yildiz, Ahmet

    2016-01-01

    SUMMARY Telomeres, repetitive DNA sequences at chromosome ends, are shielded against the DNA damage response (DDR) by the shelterin complex. To understand how shelterin protects telomere ends, we investigated the structural organization of telomeric chromatin in human cells using super-resolution microscopy. We found that telomeres form compact globular structures through a complex network of interactions between shelterin subunits and telomeric DNA, and not by DNA methylation, histone deacetylation or histone trimethylation at telomeres and subtelomeric regions. Mutations that abrogate shelterin assembly or removal of individual subunits from telomeres cause up to a 10-fold increase in telomere volume. Decompacted telomeres become more accessible to telomere-associated proteins and accumulate DDR signals. Recompaction of telomeric chromatin using an orthogonal method displaces DDR signals from telomeres. These results reveal the chromatin remodeling activity of shelterin and demonstrate that shelterin-mediated compaction of telomeric chromatin provides robust protection of chromosome ends against the DDR machinery. PMID:26871633

  1. Determination of local chromatin composition by CasID.

    Science.gov (United States)

    Schmidtmann, Elisabeth; Anton, Tobias; Rombaut, Pascaline; Herzog, Franz; Leonhardt, Heinrich

    2016-09-02

    Chromatin structure and function are determined by a plethora of proteins whose genome-wide distribution is typically assessed by immunoprecipitation (ChIP). Here, we developed a novel tool to investigate the local chromatin environment at specific DNA sequences. We combined the programmable DNA binding of dCas9 with the promiscuous biotin ligase BirA* (CasID) to biotinylate proteins in the direct vicinity of specific loci. Subsequent streptavidin-mediated precipitation and mass spectrometry identified both known and previously unknown chromatin factors associated with repetitive telomeric, major satellite and minor satellite DNA. With super-resolution microscopy, we confirmed the localization of the putative transcription factor ZNF512 at chromocenters. The versatility of CasID facilitates the systematic elucidation of functional protein complexes and locus-specific chromatin composition.

  2. Aberrant Chromatin Modification as a Mechanism of Prostate Cancer Progression

    National Research Council Canada - National Science Library

    Chen, Hongwu

    2004-01-01

    .... However, the underlying mechanism is still unclear. The purpose of this study is to test the hypothesis that aberrant chromatin modification plays a critical role in prostate cancer progression...

  3. Probing Chromatin-modifying Enzymes with Chemical Tools

    KAUST Repository

    Fischle, Wolfgang; Schwarzer, Dirk

    2016-01-01

    and represent promising drug targets in modern medicine. We summarize and discuss recent advances in the field of chemical biology that have provided chromatin research with sophisticated tools for investigating the composition, activity, and target sites

  4. FACT facilitates chromatin transcription by RNA polymerases I and III

    DEFF Research Database (Denmark)

    Birch, Joanna L; Tan, Bertrand C-M; Panov, Kostya I

    2009-01-01

    Efficient transcription elongation from a chromatin template requires RNA polymerases (Pols) to negotiate nucleosomes. Our biochemical analyses demonstrate that RNA Pol I can transcribe through nucleosome templates and that this requires structural rearrangement of the nucleosomal core particle....... The subunits of the histone chaperone FACT (facilitates chromatin transcription), SSRP1 and Spt16, co-purify and co-immunoprecipitate with mammalian Pol I complexes. In cells, SSRP1 is detectable at the rRNA gene repeats. Crucially, siRNA-mediated repression of FACT subunit expression in cells results...... in a significant reduction in 47S pre-rRNA levels, whereas synthesis of the first 40 nt of the rRNA is not affected, implying that FACT is important for Pol I transcription elongation through chromatin. FACT also associates with RNA Pol III complexes, is present at the chromatin of genes transcribed by Pol III...

  5. Neutron scattering studies on chromatin higher-order structure

    International Nuclear Information System (INIS)

    Graziano, V.; Gerchman, S.E.; Schneider, D.K.; Ramakrishnan, V.

    1994-01-01

    We have been engaged in studies of the structure and condensation of chromatin into the 30nm filament using small-angle neutron scattering. We have also used deuterated histone H1 to determine its location in the chromatin 30nm filament. Our studies indicate that chromatin condenses with increasing ionic strength to a limiting structure that has a mass per unit length of 6-7 nucleosomes/11 nm. They also show that the linker histone H1/H5 is located in the interior of the chromatin filament, in a position compatible with its binding to the inner face of the nucleosome. Analysis of the mass per unit length as a function of H5 stoichiometry suggests that 5-7 contiguous nucleosomes need to have H5 bound before a stable higher order structure can exist

  6. Citrullination regulates pluripotency and histone H1 binding to chromatin

    DEFF Research Database (Denmark)

    Christophorou, Maria A; Castelo-Branco, Gonçalo; Halley-Stott, Richard P

    2014-01-01

    citrullination of core histones has been linked to transcriptional regulation and the DNA damage response. PADI4 (also called PAD4 or PADV), the only PADI with a nuclear localization signal, was previously shown to act in myeloid cells where it mediates profound chromatin decondensation during the innate immune...... and activating their expression. Its inhibition lowers the percentage of pluripotent cells in the early mouse embryo and significantly reduces reprogramming efficiency. Using an unbiased proteomic approach we identify linker histone H1 variants, which are involved in the generation of compact chromatin, as novel...... PADI4 substrates. Citrullination of a single arginine residue within the DNA-binding site of H1 results in its displacement from chromatin and global chromatin decondensation. Together, these results uncover a role for citrullination in the regulation of pluripotency and provide new mechanistic...

  7. histone H3 predominantly mark the pericentromeric chromatin

    Indian Academy of Sciences (India)

    SANTOSH KUMAR SHARMA

    packaging of eukaryotic DNA in nucleoprotein complex known as .... The plant material used in the present study has ... materials (root tips/flower buds) were fixed in PHEMES ..... fications that mark active chromatin, while there are no data.

  8. Spatiotemporal characterization of ionizing radiation induced DNA damage foci and their relation to chromatin organization

    Energy Technology Data Exchange (ETDEWEB)

    Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard

    2009-09-15

    DNA damage sensing proteins have been shown to localize to the sites of DSB within seconds to minutes following ionizing radiation (IR) exposure, resulting in the formation of microscopically visible nuclear domains referred to as radiation-induced foci (RIF). This review characterizes the spatio-temporal properties of RIF at physiological doses, minutes to hours following exposure to ionizing radiation, and it proposes a model describing RIF formation and resolution as a function of radiation quality and nuclear densities. Discussion is limited to RIF formed by three interrelated proteins ATM (Ataxia telangiectasia mutated), 53BP1 (p53 binding protein 1) and ?H2AX (phosphorylated variant histone H2AX). Early post-IR, we propose that RIF mark chromatin reorganization, leading to a local nuclear scaffold rigid enough to keep broken DNA from diffusing away, but open enough to allow the repair machinery. We review data indicating clear kinetic and physical differences between RIF emerging from dense and uncondensed regions of the nucleus. At later time post-IR, we propose that persistent RIF observed days following exposure to ionizing radiation are nuclear ?scars? marking permanent disruption of the chromatin architecture. When DNA damage is resolved, such chromatin modifications should not necessarily lead to growth arrest and it has been shown that persistent RIF can replicate during mitosis. Thus, heritable persistent RIF spanning over tens of Mbp may affect the transcriptome of a large progeny of cells. This opens the door for a non DNA mutation-based mechanism of radiation-induced phenotypes.

  9. Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Rach

    2011-01-01

    Full Text Available The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs that occur in a narrowly defined genomic span and "dispersed" promoters with TSSs that are spread over a larger window. Previous studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, but virtually no studies have directly investigated the relationship with chromatin features. Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone variants (H2A.Z and marks (H3K4 methylation, as well as insulator binding (such as CTCF, independent of the expression levels of affected genes. Notably, differences are conserved across mammals and flies, and they provide for a clearer separation of promoter architectures than the presence and absence of CpG islands or the occurrence of stalled RNA polymerase. Computational models support the stronger contribution of chromatin features to the definition of dispersed promoters compared to focused start sites. Our results show that promoter classes defined from 5' capped transcripts not only reflect differences in the initiation process at the core promoter but also are indicative of divergent transcriptional programs established within gene-proximal nucleosome organization.

  10. From green architecture to architectural green

    DEFF Research Database (Denmark)

    Earon, Ofri

    2011-01-01

    that describes the architectural exclusivity of this particular architecture genre. The adjective green expresses architectural qualities differentiating green architecture from none-green architecture. Currently, adding trees and vegetation to the building’s facade is the main architectural characteristics...... they have overshadowed the architectural potential of green architecture. The paper questions how a green space should perform, look like and function. Two examples are chosen to demonstrate thorough integrations between green and space. The examples are public buildings categorized as pavilions. One......The paper investigates the topic of green architecture from an architectural point of view and not an energy point of view. The purpose of the paper is to establish a debate about the architectural language and spatial characteristics of green architecture. In this light, green becomes an adjective...

  11. Cytogenetic abnormality in man, wider implications of theories of sex chromatin origin.

    Science.gov (United States)

    MILES, C P

    1962-01-01

    Female nuclei may be identified by means of sex chromatin. In general the number of sex chromatin bodies is one less than the number of X chromosomes. An exception to this rule is a case of sex chromatin-positive XO Turner's syndrome. This case suggests the possibility of sex chromatin-positive XY males, and it may be evidence for chromosomal differentiation.

  12. Mechanism of chromatin degradation in thymocytes of irradiated rats

    International Nuclear Information System (INIS)

    Nikonova, L.V.; Nelipovich, P.A.; Umanskij, S.R.

    1983-01-01

    Chromatin digestion in isolated thymocyte nuclei with DNAase I, micrococcal nuclease and nuclease from Serratia marcescens was studied. It was shown that 3 h after irradiation (10 Gy), the kinetics of accumulation of acid soluble and salt soluble products of DNA degradation, caused by exogenous nucleases, remains unchanged. The administration of cycloheximide does not influence the sensitivity of chromatin to DNAase I and somewhat increases the rate of salt soluble products formation upon the nuclease from S, marcescens treatment

  13. ATP-Dependent Chromatin Remodeling Factors and Their Roles in Affecting Nucleosome Fiber Composition

    Directory of Open Access Journals (Sweden)

    Alexandra Lusser

    2011-10-01

    Full Text Available ATP-dependent chromatin remodeling factors of the SNF2 family are key components of the cellular machineries that shape and regulate chromatin structure and function. Members of this group of proteins have broad and heterogeneous functions ranging from controlling gene activity, facilitating DNA damage repair, promoting homologous recombination to maintaining genomic stability. Several chromatin remodeling factors are critical components of nucleosome assembly processes, and recent reports have identified specific functions of distinct chromatin remodeling factors in the assembly of variant histones into chromatin. In this review we will discuss the specific roles of ATP-dependent chromatin remodeling factors in determining nucleosome composition and, thus, chromatin fiber properties.

  14. Fragmentation of chromatin with 125I radioactive disintegrations

    International Nuclear Information System (INIS)

    Turner, G.N.; Nobis, P.; Dewey, W.C.

    1976-01-01

    The DNA in Chinese hamster cells was labeled first for 3 h with [ 3 H]TdR and then for 3 h with [ 125 I]UdR. Chromatin was extracted, frozen, and stored at -30 0 C until 1.0 x 10 17 and 1.25 x 10 17 disintegrations/g of labeled DNA occurred for 125 I and 3 H, respectively. Velocity sedimentation of chromatin (DNA with associated chromosomal proteins) in neutral sucrose gradients indicated that the localized energy from the 125 I disintegrations, which gave about 1 double-strand break/disintegration plus an additional 1.3 single strand breaks, selectively fragmented the [ 125 I] chromatin into pieces smaller than the [ 3 H] chromatin. In other words, 125 I disintegrations caused much more localized damage in the chromatin labeled with 125 I than in the chromatin labeled with 3 H, and fragments induced in DNA by 125 I disintegrations were not held together by the associated chromosomal proteins. Use of this 125 I technique for studying chromosomal proteins associated with different regions in the cellular DNA is discussed. For these studies, the number of disintegrations required for fragmenting DNA molecules of different sizes is illustrated

  15. Cytoplasmic chromatin triggers inflammation in senescence and cancer.

    Science.gov (United States)

    Dou, Zhixun; Ghosh, Kanad; Vizioli, Maria Grazia; Zhu, Jiajun; Sen, Payel; Wangensteen, Kirk J; Simithy, Johayra; Lan, Yemin; Lin, Yanping; Zhou, Zhuo; Capell, Brian C; Xu, Caiyue; Xu, Mingang; Kieckhaefer, Julia E; Jiang, Tianying; Shoshkes-Carmel, Michal; Tanim, K M Ahasan Al; Barber, Glen N; Seykora, John T; Millar, Sarah E; Kaestner, Klaus H; Garcia, Benjamin A; Adams, Peter D; Berger, Shelley L

    2017-10-19

    Chromatin is traditionally viewed as a nuclear entity that regulates gene expression and silencing. However, we recently discovered the presence of cytoplasmic chromatin fragments that pinch off from intact nuclei of primary cells during senescence, a form of terminal cell-cycle arrest associated with pro-inflammatory responses. The functional significance of chromatin in the cytoplasm is unclear. Here we show that cytoplasmic chromatin activates the innate immunity cytosolic DNA-sensing cGAS-STING (cyclic GMP-AMP synthase linked to stimulator of interferon genes) pathway, leading both to short-term inflammation to restrain activated oncogenes and to chronic inflammation that associates with tissue destruction and cancer. The cytoplasmic chromatin-cGAS-STING pathway promotes the senescence-associated secretory phenotype in primary human cells and in mice. Mice deficient in STING show impaired immuno-surveillance of oncogenic RAS and reduced tissue inflammation upon ionizing radiation. Furthermore, this pathway is activated in cancer cells, and correlates with pro-inflammatory gene expression in human cancers. Overall, our findings indicate that genomic DNA serves as a reservoir to initiate a pro-inflammatory pathway in the cytoplasm in senescence and cancer. Targeting the cytoplasmic chromatin-mediated pathway may hold promise in treating inflammation-related disorders.

  16. Epigenetic regulation of open chromatin in pluripotent stem cells

    Science.gov (United States)

    Kobayashi, Hiroshi; Kikyo, Nobuaki

    2014-01-01

    The recent progress in pluripotent stem cell research has opened new avenues of disease modeling, drug screening, and transplantation of patient-specific tissues that had been unimaginable until a decade ago. The central mechanism underlying pluripotency is epigenetic gene regulation; the majority of cell signaling pathways, both extracellular and cytoplasmic, eventually alter the epigenetic status of their target genes during the process of activating or suppressing the genes to acquire or maintain pluripotency. It has long been thought that the chromatin of pluripotent stem cells is globally open to enable the timely activation of essentially all genes in the genome during differentiation into multiple lineages. The current article reviews descriptive observations and the epigenetic machinery relevant to what is supposed to be globally open chromatin in pluripotent stem cells. This includes microscopic appearance, permissive gene transcription, chromatin remodeling complexes, histone modifications, DNA methylation, noncoding RNAs, dynamic movement of chromatin proteins, nucleosome accessibility and positioning, and long-range chromosomal interactions. Detailed analyses of each element, however, have revealed that the globally open chromatin hypothesis is not necessarily supported by some of the critical experimental evidence, such as genome-wide nucleosome accessibility and nucleosome positioning. Further understanding of the epigenetic gene regulation is expected to determine the true nature of the so-called globally open chromatin in pluripotent stem. PMID:24695097

  17. Chromatin modifications and the DNA damage response to ionizing radiation

    International Nuclear Information System (INIS)

    Kumar, Rakesh; Horikoshi, Nobuo; Singh, Mayank; Gupta, Arun; Misra, Hari S.; Albuquerque, Kevin; Hunt, Clayton R.; Pandita, Tej K.

    2013-01-01

    In order to survive, cells have evolved highly effective repair mechanisms to deal with the potentially lethal DNA damage produced by exposure to endogenous as well as exogenous agents. Ionizing radiation exposure induces highly lethal DNA damage, especially DNA double-strand breaks (DSBs), that is sensed by the cellular machinery and then subsequently repaired by either of two different DSB repair mechanisms: (1) non-homologous end joining, which re-ligates the broken ends of the DNA and (2) homologous recombination, that employs an undamaged identical DNA sequence as a template, to maintain the fidelity of DNA repair. Repair of DSBs must occur within the natural context of the cellular DNA which, along with specific proteins, is organized to form chromatin, the overall structure of which can impede DNA damage site access by repair proteins. The chromatin complex is a dynamic structure and is known to change as required for ongoing cellular processes such as gene transcription or DNA replication. Similarly, during the process of DNA damage sensing and repair, chromatin needs to undergo several changes in order to facilitate accessibility of the repair machinery. Cells utilize several factors to modify the chromatin in order to locally open up the structure to reveal the underlying DNA sequence but post-translational modification of the histone components is one of the primary mechanisms. In this review, we will summarize chromatin modifications by the respective chromatin modifying factors that occur during the DNA damage response.

  18. MUF architecture /art London

    DEFF Research Database (Denmark)

    Svenningsen Kajita, Heidi

    2009-01-01

    Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art......Om MUF architecture samt interview med Liza Fior og Katherine Clarke, partnere i muf architecture/art...

  19. Argonaute2 and LaminB modulate gene expression by controlling chromatin topology.

    Directory of Open Access Journals (Sweden)

    Ezequiel Nazer

    2018-03-01

    Full Text Available Drosophila Argonaute2 (AGO2 has been shown to regulate expression of certain loci in an RNA interference (RNAi-independent manner, but its genome-wide function on chromatin remains unknown. Here, we identified the nuclear scaffolding protein LaminB as a novel interactor of AGO2. When either AGO2 or LaminB are depleted in Kc cells, similar transcription changes are observed genome-wide. In particular, changes in expression occur mainly in active or potentially active chromatin, both inside and outside LaminB-associated domains (LADs. Furthermore, we identified a somatic target of AGO2 transcriptional repression, no hitter (nht, which is immersed in a LAD located within a repressive topologically-associated domain (TAD. Null mutation but not catalytic inactivation of AGO2 leads to ectopic expression of nht and downstream spermatogenesis genes. Depletion of either AGO2 or LaminB results in reduced looping interactions within the nht TAD as well as ectopic inter-TAD interactions, as detected by 4C-seq analysis. Overall, our findings reveal coordination of AGO2 and LaminB function to dictate genome architecture and thereby regulate gene expression.

  20. Architectural fragments

    DEFF Research Database (Denmark)

    Bang, Jacob Sebastian

    2018-01-01

    I have created a large collection of plaster models: a collection of Obstructions, errors and opportunities that may develop into architecture. The models are fragments of different complex shapes as well as more simple circular models with different profiling and diameters. In this contect I have....... I try to invent the ways of drawing the models - that decode and unfold them into architectural fragments- into future buildings or constructions in the landscape. [1] Luigi Moretti: Italian architect, 1907 - 1973 [2] Man Ray: American artist, 1890 - 1976. in 2015, I saw the wonderful exhibition...... "Man Ray - Human Equations" at the Glyptotek in Copenhagen, organized by the Philips Collection in Washington D.C. and the Israel Museum in Jerusalem (in 2013). See also: "Man Ray - Human Equations" catalogue published by Hatje Cantz Verlag, Germany, 2014....

  1. Kosmos = architecture

    Directory of Open Access Journals (Sweden)

    Tine Kurent

    1985-12-01

    Full Text Available The old Greek word "kosmos" means not only "cosmos", but also "the beautiful order", "the way of building", "building", "scenography", "mankind", and, in the time of the New Testament, also "pagans". The word "arhitekton", meaning first the "master of theatrical scenography", acquired the meaning of "builder", when the words "kosmos" and ~kosmetes" became pejorative. The fear that architecture was not considered one of the arts before Renaissance, since none of the Muses supervised the art of building, results from the misunderstanding of the word "kosmos". Urania was the Goddes of the activity implied in the verb "kosmein", meaning "to put in the beautiful order" - everything, from the universe to the man-made space, i. e. the architecture.

  2. Metabolistic Architecture

    DEFF Research Database (Denmark)

    2013-01-01

    Textile Spaces presents different approaches to using textile as a spatial definer and artistic medium. The publication collages images and text, art and architecture, science, philosophy and literature, process and product, past, present and future. It forms an insight into soft materials' funct......' functional and poetic potentials, linking the disciplines through fragments that aim to inspire a further look into the artists' and architects' practices, while simultaneously framing these textile visions in a wider context.......Textile Spaces presents different approaches to using textile as a spatial definer and artistic medium. The publication collages images and text, art and architecture, science, philosophy and literature, process and product, past, present and future. It forms an insight into soft materials...

  3. Interphase Chromosome Conformation and Chromatin-Chromatin Interactions in Human Epithelial Cells Cultured Under Different Gravity Conditions

    Science.gov (United States)

    Zhang, Ye; Wong, Michael; Hada, Megumi; Wu, Honglu

    2015-01-01

    Microgravity has been shown to alter global gene expression patterns and protein levels both in cultured cells and animal models. It has been suggested that the packaging of chromatin fibers in the interphase nucleus is closely related to genome function, and the changes in transcriptional activity are tightly correlated with changes in chromatin folding. This study explores the changes of chromatin conformation and chromatin-chromatin interactions in the simulated microgravity environment, and investigates their correlation to the expression of genes located at different regions of the chromosome. To investigate the folding of chromatin in interphase under various culture conditions, human epithelial cells, fibroblasts, and lymphocytes were fixed in the G1 phase. Interphase chromosomes were hybridized with a multicolor banding in situ hybridization (mBAND) probe for chromosome 3 which distinguishes six regions of the chromosome as separate colors. After images were captured with a laser scanning confocal microscope, the 3-dimensional structure of interphase chromosome 3 was reconstructed at multi-mega base pair scale. In order to determine the effects of microgravity on chromosome conformation and orientation, measures such as distance between homologous pairs, relative orientation of chromosome arms about a shared midpoint, and orientation of arms within individual chromosomes were all considered as potentially impacted by simulated microgravity conditions. The studies revealed non-random folding of chromatin in interphase, and suggested an association of interphase chromatin folding with radiation-induced chromosome aberration hotspots. Interestingly, the distributions of genes with expression changes over chromosome 3 in cells cultured under microgravity environment are apparently clustered on specific loci and chromosomes. This data provides important insights into how mammalian cells respond to microgravity at molecular level.

  4. Distribution of segmental duplications in the context of higher order chromatin organisation of human chromosome 7

    DEFF Research Database (Denmark)

    Ebert, Grit; Steininger, Anne; Weißmann, Robert

    2014-01-01

    of the Williams-Beuren syndrome locus we demonstrate by cross-species comparison that these SDs have inserted at the borders of a topological domain and that they flank regions with distinct DNA conformation. CONCLUSIONS: Our study suggests a link of nuclear architecture and the propagation of SDs across......BACKGROUND: Segmental duplications (SDs) are not evenly distributed along chromosomes. The reasons for this biased susceptibility to SD insertion are poorly understood. Accumulation of SDs is associated with increased genomic instability, which can lead to structural variants and genomic disorders...... chromosome 7, either by promoting regional SD insertion or by contributing to the establishment of higher order chromatin organisation themselves. The latter could compensate for the high risk of structural rearrangements and thus may have contributed to their evolutionary fixation in the human genome....

  5. Connecting Architecture and Implementation

    Science.gov (United States)

    Buchgeher, Georg; Weinreich, Rainer

    Software architectures are still typically defined and described independently from implementation. To avoid architectural erosion and drift, architectural representation needs to be continuously updated and synchronized with system implementation. Existing approaches for architecture representation like informal architecture documentation, UML diagrams, and Architecture Description Languages (ADLs) provide only limited support for connecting architecture descriptions and implementations. Architecture management tools like Lattix, SonarJ, and Sotoarc and UML-tools tackle this problem by extracting architecture information directly from code. This approach works for low-level architectural abstractions like classes and interfaces in object-oriented systems but fails to support architectural abstractions not found in programming languages. In this paper we present an approach for linking and continuously synchronizing a formalized architecture representation to an implementation. The approach is a synthesis of functionality provided by code-centric architecture management and UML tools and higher-level architecture analysis approaches like ADLs.

  6. Circadian expression profiles of chromatin remodeling factor genes in Arabidopsis.

    Science.gov (United States)

    Lee, Hong Gil; Lee, Kyounghee; Jang, Kiyoung; Seo, Pil Joon

    2015-01-01

    The circadian clock is a biological time keeper mechanism that regulates biological rhythms to a period of approximately 24 h. The circadian clock enables organisms to anticipate environmental cycles and coordinates internal cellular physiology with external environmental cues. In plants, correct matching of the clock with the environment confers fitness advantages to plant survival and reproduction. Therefore, circadian clock components are regulated at multiple layers to fine-tune the circadian oscillation. Epigenetic regulation provides an additional layer of circadian control. However, little is known about which chromatin remodeling factors are responsible for circadian control. In this work, we analyzed circadian expression of 109 chromatin remodeling factor genes and identified 17 genes that display circadian oscillation. In addition, we also found that a candidate interacts with a core clock component, supporting that clock activity is regulated in part by chromatin modification. As an initial attempt to elucidate the relationship between chromatin modification and circadian oscillation, we identified novel regulatory candidates that provide a platform for future investigations of chromatin regulation of the circadian clock.

  7. Oxidative stress signaling to chromatin in health and disease

    KAUST Repository

    Kreuz, Sarah

    2016-06-20

    Oxidative stress has a significant impact on the development and progression of common human pathologies, including cancer, diabetes, hypertension and neurodegenerative diseases. Increasing evidence suggests that oxidative stress globally influences chromatin structure, DNA methylation, enzymatic and non-enzymatic post-translational modifications of histones and DNA-binding proteins. The effects of oxidative stress on these chromatin alterations mediate a number of cellular changes, including modulation of gene expression, cell death, cell survival and mutagenesis, which are disease-driving mechanisms in human pathologies. Targeting oxidative stress-dependent pathways is thus a promising strategy for the prevention and treatment of these diseases. We summarize recent research developments connecting oxidative stress and chromatin regulation.

  8. Higher-order structure of Saccharomyces cerevisiae chromatin

    International Nuclear Information System (INIS)

    Lowary, P.T.; Widom, J.

    1989-01-01

    We have developed a method for partially purifying chromatin from Saccharomyces cerevisiae (baker's yeast) to a level suitable for studies of its higher-order folding. This has required the use of yeast strains that are free of the ubiquitous yeast killer virus. Results from dynamic light scattering, electron microscopy, and x-ray diffraction show that the yeast chromatin undergoes a cation-dependent folding into 30-nm filaments that resemble those characteristic of higher-cell chromatin; moreover, the packing of nucleosomes within the yeast 30-nm filaments is similar to that of higher cells. These results imply that yeast has a protein or protein domain that serves the role of the histone H 1 found in higher cells; physical and genetic studies of the yeast activity could help elucidate the structure and function of H 1. Images of the yeast 30-nm filaments can be used to test crossed-linker models for 30-nm filament structure

  9. Chromatin Regulation and the Histone Code in HIV Latency
.

    Science.gov (United States)

    Turner, Anne-Marie W; Margolis, David M

    2017-06-01

    The formation of a latent reservoir of Human Immunodeficiency Virus (HIV) infection hidden from immune clearance remains a significant obstacle to approaches to eradicate HIV infection. Towards an understanding of the mechanisms of HIV persistence, there is a growing body of work implicating epigenetic regulation of chromatin in establishment and maintenance of this latent reservoir. Here we discuss recent advances in the field of chromatin regulation, specifically in our understanding of the histone code, and how these discoveries relate to our current knowledge of the chromatin mechanisms linked to HIV transcriptional repression and the reversal of latency. We also examine mechanisms unexplored in the context of HIV latency and briefly discuss current therapies aimed at the induction of proviral expression within latently infected cells. We aim to emphasize that a greater understanding of the epigenetic mechanisms which govern HIV latency could lead to new therapeutic targets for latency reversal and clearance cure strategies.

  10. Fast neutron biological effects on normal and tumor chromatin

    International Nuclear Information System (INIS)

    Constantinescu, B.; Bugoi, Roxana; Paunica, Tatiana; Radu, Liliana

    1997-01-01

    Growing interest in neutron therapy and radioprotection requires complex studies on the mechanisms of neutron action on biological systems, especially on chromatin (the complex of deoxyribonucleic acid-DNA- with proteins in eukaryotic cells). Our study aims to investigate the fast neutrons induced damages in normal and tumor chromatin, studying thermal transition, intrinsic fluorescence and fluorescence of chromatin-ethidium bromide complexes behavior versus irradiation dose. The Bucharest U-120 variable energy Cyclotron was employed as an intense source of fast neutrons produced by 13.5 MeV deuterons on a thick beryllium target (166.5 mg/cm 2 ) placed at 20 angle against the incident beam. The average energy is 5.24 MeV. The total yield at 0 angle is 6.7 x 10 16 n/sr·C·MeV. To determine neutron and gamma irradiation doses, home made thermoluminescent detectors-TLD(γ) and TLD (γ + n) were used: for gamma MgF 2 : Mn mixed with Teflon pellets (φ 12.5 mm, 0.6±0.1 mm thick) and for gamma plus neutrons MgF 2 :Mn mixed with 6 LiF and Teflon pellets (same dimensions). Using a 8.022 x 10 -2 albedo factor value and the equivalence 1Gy (n)=2·10 10 fast neutron/cm 2 , the dose for the irradiation of 1.2 x 10 2 Gy/μC, with an estimated precision of 15% C for neutrons and 7.8 x 10 -4 Gy/μC for gamma, at 10 cm behind Be target, was found, respectively. A diminution of the negative fluorescence intensity for chromatin-ethidium bromide complexes with the increasing of neutron dose (from 0.98 at 5 Gy to 0.85 at 100 Gy) was observed for normal chromatin. This fact reflects chromatin DNA injuries, with the decrease of double helix DNA proportion. To study the influence of gyrostan, thyroxine and D3 vitamin treatments on fast neutron radiolysis in tumor chromatin,10 mg/kg of anticancer drug gyrostan, 40μg/kg of hormonal compound thyroxine and 30,000 IU/kg of D3 vitamin were administrated, separately or associated, to Wistar rats bearing Walker carcinosarcoma. Representing

  11. Radiation-induced cell death by chromatin loss

    International Nuclear Information System (INIS)

    Campbell, I.R.; Warenius, H.M.

    1989-01-01

    A model is proposed which relates reproductive death of cells caused by radiation to loss of chromatin at cell division. This loss of chromatin can occur through chromosomal deletions or through the formation of asymmetrical chromosomal exchanges. It is proposed that smaller doses of radiation produce fewer chromatin breaks, which are more likely to be accurately repaired, compared with larger doses. Consequently, smaller doses of radiation are less efficient in causing cell death, leading to a shoulder on the cell survival curve. Experimental evidence supports this model, and the fit between the derived formula and experimental cell survival curves is good. The derived formula approximates to the linear-quadratic equation at low doses of radiation. (author)

  12. INO80 Chromatin Remodeling Coordinates Metabolic Homeostasis with Cell Division

    Directory of Open Access Journals (Sweden)

    Graeme J. Gowans

    2018-01-01

    Full Text Available Adaptive survival requires the coordination of nutrient availability with expenditure of cellular resources. For example, in nutrient-limited environments, 50% of all S. cerevisiae genes synchronize and exhibit periodic bursts of expression in coordination with respiration and cell division in the yeast metabolic cycle (YMC. Despite the importance of metabolic and proliferative synchrony, the majority of YMC regulators are currently unknown. Here, we demonstrate that the INO80 chromatin-remodeling complex is required to coordinate respiration and cell division with periodic gene expression. Specifically, INO80 mutants have severe defects in oxygen consumption and promiscuous cell division that is no longer coupled with metabolic status. In mutant cells, chromatin accessibility of periodic genes, including TORC1-responsive genes, is relatively static, concomitant with severely attenuated gene expression. Collectively, these results reveal that the INO80 complex mediates metabolic signaling to chromatin to restrict proliferation to metabolically optimal states.

  13. N-Butyrate alters chromatin accessibility to DNA repair enzymes

    International Nuclear Information System (INIS)

    Smith, P.J.

    1986-01-01

    Current evidence suggests that the complex nature of mammalian chromatin can result in the concealment of DNA damage from repair enzymes and their co-factors. Recently it has been proposed that the acetylation of histone proteins in chromatin may provide a surveillance system whereby damaged regions of DNA become exposed due to changes in chromatin accessibility. This hypothesis has been tested by: (i) using n-butyrate to induce hyperacetylation in human adenocarcinoma (HT29) cells; (ii) monitoring the enzymatic accessibility of chromatin in permeabilised cells; (iii) measuring u.v. repair-associated nicking of DNA in intact cells and (iv) determining the effects of n-butyrate on cellular sensitivity to DNA damaging agents. The results indicate that the accessibility of chromatin to Micrococcus luteus u.v. endonuclease is enhanced by greater than 2-fold in n-butyrate-treated cells and that there is a corresponding increase in u.v. repair incision rates in intact cells exposed to the drug. Non-toxic levels of n-butyrate induce a block to G1 phase transit and there is a significant growth delay on removal of the drug. Resistance of HT29 cells to u.v.-radiation and adriamycin is enhanced in n-butyrate-treated cells whereas X-ray sensitivity is increased. Although changes in the responses of cells to DNA damaging agents must be considered in relation to the effects of n-butyrate on growth rate and cell-cycle distribution, the results are not inconsistent with the proposal that increased enzymatic-accessibility/repair is biologically favourable for the resistance of cells to u.v.-radiation damage. Overall the results support the suggested operation of a histone acetylation-based chromatin surveillance system in human cells

  14. Architectural Drawing

    DEFF Research Database (Denmark)

    Steinø, Nicolai

    2018-01-01

    In a time of computer aided design, computer graphics and parametric design tools, the art of architectural drawing is in a state of neglect. But design and drawing are inseparably linked in ways which often go unnoticed. Essentially, it is very difficult, if not impossible, to conceive of a design...... is that computers can represent graphic ideas both faster and better than most medium-skilled draftsmen, drawing in design is not only about representing final designs. In fact, several steps involving the capacity to draw lie before the representation of a final design. Not only is drawing skills an important...... prerequisite for learning about the nature of existing objects and spaces, and thus to build a vocabulary of design. It is also a prerequisite for both reflecting and communicating about design ideas. In this paper, a taxonomy of notation, reflection, communication and presentation drawing is presented...

  15. Architectural Theatricality

    DEFF Research Database (Denmark)

    Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning

    2013-01-01

    In the attempt to improve patient treatment and recovery, researchers focus on applying concepts of hospitality to hospitals. Often these concepts are dominated by hotel-metaphors focusing on host–guest relationships or concierge services. Motivated by a project trying to improve patient treatment...... is known for his writings on theatricality, understood as a holistic design approach emphasizing the contextual, cultural, ritual and social meanings rooted in architecture. Relative hereto, the International Food Design Society recently argued, in a similar holistic manner, that the methodology used...... to provide an aesthetic eating experience includes knowledge on both food and design. Based on a hermeneutic reading of Semper’s theory, our thesis is that this holistic design approach is important when debating concepts of hospitality in hospitals. We use this approach to argue for how ‘food design...

  16. Lab architecture

    Science.gov (United States)

    Crease, Robert P.

    2008-04-01

    There are few more dramatic illustrations of the vicissitudes of laboratory architecturethan the contrast between Building 20 at the Massachusetts Institute of Technology (MIT) and its replacement, the Ray and Maria Stata Center. Building 20 was built hurriedly in 1943 as temporary housing for MIT's famous Rad Lab, the site of wartime radar research, and it remained a productive laboratory space for over half a century. A decade ago it was demolished to make way for the Stata Center, an architecturally striking building designed by Frank Gehry to house MIT's computer science and artificial intelligence labs (above). But in 2004 - just two years after the Stata Center officially opened - the building was criticized for being unsuitable for research and became the subject of still ongoing lawsuits alleging design and construction failures.

  17. Chromatin structure and evolution in the human genome

    Directory of Open Access Journals (Sweden)

    Dunlop Malcolm G

    2007-05-01

    Full Text Available Abstract Background Evolutionary rates are not constant across the human genome but genes in close proximity have been shown to experience similar levels of divergence and selection. The higher-order organisation of chromosomes has often been invoked to explain such phenomena but previously there has been insufficient data on chromosome structure to investigate this rigorously. Using the results of a recent genome-wide analysis of open and closed human chromatin structures we have investigated the global association between divergence, selection and chromatin structure for the first time. Results In this study we have shown that, paradoxically, synonymous site divergence (dS at non-CpG sites is highest in regions of open chromatin, primarily as a result of an increased number of transitions, while the rates of other traditional measures of mutation (intergenic, intronic and ancient repeat divergence as well as SNP density are highest in closed regions of the genome. Analysis of human-chimpanzee divergence across intron-exon boundaries indicates that although genes in relatively open chromatin generally display little selection at their synonymous sites, those in closed regions show markedly lower divergence at their fourfold degenerate sites than in neighbouring introns and intergenic regions. Exclusion of known Exonic Splice Enhancer hexamers has little affect on the divergence observed at fourfold degenerate sites across chromatin categories; however, we show that closed chromatin is enriched with certain classes of ncRNA genes whose RNA secondary structure may be particularly important. Conclusion We conclude that, overall, non-CpG mutation rates are lowest in open regions of the genome and that regions of the genome with a closed chromatin structure have the highest background mutation rate. This might reflect lower rates of DNA damage or enhanced DNA repair processes in regions of open chromatin. Our results also indicate that dS is a poor

  18. Model for the structure of the active nucleolar chromatin

    International Nuclear Information System (INIS)

    Labhart, P.; Ness, P.; Banz, E.; Parish, R.; Koller, T.; Universitaet Zurich, Switzerland)

    1983-01-01

    Transcribed ribosomal genes of Xenopus laevis oocytes and of Dictyostelium discoideum were studied electron microscopically using step gradients at different ionic strengths. Under these conditions the fiber of the active chromatin appears smooth and is indistinguishable from free DNA. The accessibility of the coding region and of a nontranscribed spacer region to restriction enzymes and micrococcal nuclease were investigated. All of the results obtained are consistent with a model in which active nucleolar chromatin is mostly composed of free DNA and the components required for transcription. 50 references, 7 figures

  19. Chromatin versus pathogens: the function of epigenetics in plant immunity

    Science.gov (United States)

    Ding, Bo; Wang, Guo-Liang

    2015-01-01

    To defend against pathogens, plants have developed a sophisticated innate immunity that includes effector recognition, signal transduction, and rapid defense responses. Recent evidence has demonstrated that plants utilize the epigenetic control of gene expression to fine-tune their defense when challenged by pathogens. In this review, we highlight the current understanding of the molecular mechanisms of histone modifications (i.e., methylation, acetylation, and ubiquitination) and chromatin remodeling that contribute to plant immunity against pathogens. Functions of key histone-modifying and chromatin remodeling enzymes are discussed. PMID:26388882

  20. Chromatin Structure of Epstein-Barr Virus Latent Episomes.

    Science.gov (United States)

    Lieberman, Paul M

    2015-01-01

    EBV latent infection is characterized by a highly restricted pattern of viral gene expression. EBV can establish latent infections in multiple different tissue types with remarkable variation and plasticity in viral transcription and replication. During latency, the viral genome persists as a multi-copy episome, a non-integrated-closed circular DNA with nucleosome structure similar to cellular chromosomes. Chromatin assembly and histone modifications contribute to the regulation of viral gene expression, DNA replication, and episome persistence during latency. This review focuses on how EBV latency is regulated by chromatin and its associated processes.

  1. A Method to Identify Nucleolus-Associated Chromatin Domains (NADs).

    Science.gov (United States)

    Carpentier, Marie-Christine; Picart-Picolo, Ariadna; Pontvianne, Frédéric

    2018-01-01

    The nuclear context needs to be taken into consideration to better understand the mechanisms shaping the epigenome and its organization, and therefore its impact on gene expression. For example, in Arabidopsis, heterochromatin is preferentially localized at the nuclear and the nucleolar periphery. Although chromatin domains associating with the nuclear periphery remain to be identified in plant cells, Nucleolus Associated chromatin Domains (NADs) can be identified thanks to a protocol allowing the isolation of pure nucleoli. We describe here the protocol enabling the identification of NADs in Arabidopsis. Providing the transfer of a nucleolus marker as described here in other crop species, this protocol is broadly applicable.

  2. The importance of topoisomerases for chromatin regulated genes

    DEFF Research Database (Denmark)

    Fredsøe, Jacob Christian; Pedersen, Jakob Madsen; Rødgaard, Morten Terpager

    2013-01-01

    DNA topoisomerases are enzymes, which function to relieve torsional stress in the DNA helix by introducing transient breaks into the DNA molecule. By use of Saccharomyces cerevisiae and microarray technology we have previously shown that topoisomerases are required for the activation of chromatin...... topoisomerases for optimal activation, but in contrast to the PHO5 gene, topoisomerases are not required for chromatin remodeling of the GAL1/10 promoter region, indicating a different role of the enzymes. We are currently performing a detailed investigation of the GAL genes to elucidate the precise role...

  3. Retention of the Native Epigenome in Purified Mammalian Chromatin.

    Directory of Open Access Journals (Sweden)

    Andreas H Ehrensberger

    Full Text Available A protocol is presented for the isolation of native mammalian chromatin as fibers of 25-250 nucleosomes under conditions that preserve the natural epigenetic signature. The material is composed almost exclusively of histones and DNA and conforms to the structure expected by electron microscopy. All sequences probed for were retained, indicating that the material is representative of the majority of the genome. DNA methylation marks and histone marks resembled the patterns observed in vivo. Importantly, nucleosome positions also remained largely unchanged, except on CpG islands, where nucleosomes were found to be unstable. The technical challenges of reconstituting biochemical reactions with native mammalian chromatin are discussed.

  4. Chromatin remodelling: the industrial revolution of DNA around histones.

    Science.gov (United States)

    Saha, Anjanabha; Wittmeyer, Jacqueline; Cairns, Bradley R

    2006-06-01

    Chromatin remodellers are specialized multi-protein machines that enable access to nucleosomal DNA by altering the structure, composition and positioning of nucleosomes. All remodellers have a catalytic ATPase subunit that is similar to known DNA-translocating motor proteins, suggesting DNA translocation as a unifying aspect of their mechanism. Here, we explore the diversity and specialization of chromatin remodellers, discuss how nucleosome modifications regulate remodeller activity and consider a model for the exposure of nucleosomal DNA that involves the use of directional DNA translocation to pump 'DNA waves' around the nucleosome.

  5. Do chromatin changes around a nascent double strand DNA break spread spherically into linearly non-adjacent chromatin?

    Science.gov (United States)

    Savic, Velibor

    2013-01-01

    In the last decade, a lot has been done in elucidating the sequence of events that occur at the nascent double strand DNA break. Nevertheless, the overall structure formed by the DNA damage response (DDR) factors around the break site, the repair focus, remains poorly understood. Although most of the data presented so far only address events that occur in chromatin in cis around the break, there are strong indications that in mammalian systems it may also occur in trans, analogous to the recent findings showing this if budding yeast. There have been attempts to address the issue but the final proof is still missing due to lack of a proper experimental system. If found to be true, the spatial distribution of DDR factors would have a major impact on the neighboring chromatin both in cis and in trans, significantly affecting local chromatin function; gene transcription and potentially other functions.

  6. Activating RNAs associate with Mediator to enhance chromatin architecture and transcription

    OpenAIRE

    Lai, Fan; Orom, Ulf A; Cesaroni, Matteo; Beringer, Malte; Taatjes, Dylan J; Blobel, Gerd A.; Shiekhattar, Ramin

    2013-01-01

    Recent advances in genomic research have revealed the existence of a large number of transcripts devoid of protein-coding potential in multiple organisms 1-8 . While the functional role for long non-coding RNAs (lncRNAs) has been best defined in epigenetic phenomena such as X inactivation and imprinting, different classes of lncRNAs may have varied biological functions 8-13 . We and others have identified a class of lncRNAs, termed ncRNA-activating (ncRNA-a), that function to activate their n...

  7. Using DNase Hi-C techniques to map global and local three-dimensional genome architecture at high resolution.

    Science.gov (United States)

    Ma, Wenxiu; Ay, Ferhat; Lee, Choli; Gulsoy, Gunhan; Deng, Xinxian; Cook, Savannah; Hesson, Jennifer; Cavanaugh, Christopher; Ware, Carol B; Krumm, Anton; Shendure, Jay; Blau, C Anthony; Disteche, Christine M; Noble, William S; Duan, ZhiJun

    2018-06-01

    The folding and three-dimensional (3D) organization of chromatin in the nucleus critically impacts genome function. The past decade has witnessed rapid advances in genomic tools for delineating 3D genome architecture. Among them, chromosome conformation capture (3C)-based methods such as Hi-C are the most widely used techniques for mapping chromatin interactions. However, traditional Hi-C protocols rely on restriction enzymes (REs) to fragment chromatin and are therefore limited in resolution. We recently developed DNase Hi-C for mapping 3D genome organization, which uses DNase I for chromatin fragmentation. DNase Hi-C overcomes RE-related limitations associated with traditional Hi-C methods, leading to improved methodological resolution. Furthermore, combining this method with DNA capture technology provides a high-throughput approach (targeted DNase Hi-C) that allows for mapping fine-scale chromatin architecture at exceptionally high resolution. Hence, targeted DNase Hi-C will be valuable for delineating the physical landscapes of cis-regulatory networks that control gene expression and for characterizing phenotype-associated chromatin 3D signatures. Here, we provide a detailed description of method design and step-by-step working protocols for these two methods. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Different nucleosomal architectures at early and late replicating origins in Saccharomyces cerevisiae.

    Science.gov (United States)

    Soriano, Ignacio; Morafraile, Esther C; Vázquez, Enrique; Antequera, Francisco; Segurado, Mónica

    2014-09-13

    Eukaryotic genomes are replicated during S phase according to a temporal program. Several determinants control the timing of origin firing, including the chromatin environment and epigenetic modifications. However, how chromatin structure influences the timing of the activation of specific origins is still poorly understood. By performing high-resolution analysis of genome-wide nucleosome positioning we have identified different chromatin architectures at early and late replication origins. These different patterns are already established in G1 and are tightly correlated with the organization of adjacent transcription units. Moreover, specific early and late nucleosomal patterns are fixed robustly, even in rpd3 mutants in which histone acetylation and origin timing have been significantly altered. Nevertheless, higher histone acetylation levels correlate with the local modulation of chromatin structure, leading to increased origin accessibility. In addition, we conducted parallel analyses of replication and nucleosome dynamics that revealed that chromatin structure at origins is modulated during origin activation. Our results show that early and late replication origins present distinctive nucleosomal configurations, which are preferentially associated to different genomic regions. Our data also reveal that origin structure is dynamic and can be locally modulated by histone deacetylation, as well as by origin activation. These data offer novel insight into the contribution of chromatin structure to origin selection and firing in budding yeast.

  9. De novo prediction of human chromosome structures: Epigenetic marking patterns encode genome architecture.

    Science.gov (United States)

    Di Pierro, Michele; Cheng, Ryan R; Lieberman Aiden, Erez; Wolynes, Peter G; Onuchic, José N

    2017-11-14

    Inside the cell nucleus, genomes fold into organized structures that are characteristic of cell type. Here, we show that this chromatin architecture can be predicted de novo using epigenetic data derived from chromatin immunoprecipitation-sequencing (ChIP-Seq). We exploit the idea that chromosomes encode a 1D sequence of chromatin structural types. Interactions between these chromatin types determine the 3D structural ensemble of chromosomes through a process similar to phase separation. First, a neural network is used to infer the relation between the epigenetic marks present at a locus, as assayed by ChIP-Seq, and the genomic compartment in which those loci reside, as measured by DNA-DNA proximity ligation (Hi-C). Next, types inferred from this neural network are used as an input to an energy landscape model for chromatin organization [Minimal Chromatin Model (MiChroM)] to generate an ensemble of 3D chromosome conformations at a resolution of 50 kilobases (kb). After training the model, dubbed Maximum Entropy Genomic Annotation from Biomarkers Associated to Structural Ensembles (MEGABASE), on odd-numbered chromosomes, we predict the sequences of chromatin types and the subsequent 3D conformational ensembles for the even chromosomes. We validate these structural ensembles by using ChIP-Seq tracks alone to predict Hi-C maps, as well as distances measured using 3D fluorescence in situ hybridization (FISH) experiments. Both sets of experiments support the hypothesis of phase separation being the driving process behind compartmentalization. These findings strongly suggest that epigenetic marking patterns encode sufficient information to determine the global architecture of chromosomes and that de novo structure prediction for whole genomes may be increasingly possible. Copyright © 2017 the Author(s). Published by PNAS.

  10. SUSTAINABLE ARCHITECTURE : WHAT ARCHITECTURE STUDENTS THINK

    OpenAIRE

    SATWIKO, PRASASTO

    2013-01-01

    Sustainable architecture has become a hot issue lately as the impacts of climate change become more intense. Architecture educations have responded by integrating knowledge of sustainable design in their curriculum. However, in the real life, new buildings keep coming with designs that completely ignore sustainable principles. This paper discusses the results of two national competitions on sustainable architecture targeted for architecture students (conducted in 2012 and 2013). The results a...

  11. Large-scale Comparative Study of Hi-C-based Chromatin 3D Structure Modeling Methods

    KAUST Repository

    Wang, Cheng

    2018-01-01

    Chromatin is a complex polymer molecule in eukaryotic cells, primarily consisting of DNA and histones. Many works have shown that the 3D folding of chromatin structure plays an important role in DNA expression. The recently proposed Chro- mosome

  12. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2003-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  13. Testing Whether Defective Chromatin Assembly in S-Phase Contributes to Breast Cancer

    National Research Council Canada - National Science Library

    Adams, Peter

    2004-01-01

    .... We used a dominant negative mutant of (chromatin assembly factor-I) CAF1, a complex that assembles newly synthesized DNA into nucleosomes, to inhibit S-phase chromatin assembly and found that this induced S-phase arrest...

  14. Relationship between chromatin structure and sensitivity to molecularly targeted auger electron radiation therapy.

    NARCIS (Netherlands)

    Terry, S.Y.A.; Vallis, K.A.

    2012-01-01

    PURPOSE: The open structure of euchromatin renders it susceptible to DNA damage by ionizing radiation (IR) compared with compact heterochromatin. The effect of chromatin configuration on the efficacy of Auger electron radiotherapy was investigated. METHODS AND MATERIALS: Chromatin structure was

  15. Modeling Architectural Patterns Using Architectural Primitives

    NARCIS (Netherlands)

    Zdun, Uwe; Avgeriou, Paris

    2005-01-01

    Architectural patterns are a key point in architectural documentation. Regrettably, there is poor support for modeling architectural patterns, because the pattern elements are not directly matched by elements in modeling languages, and, at the same time, patterns support an inherent variability that

  16. Software architecture 2

    CERN Document Server

    Oussalah, Mourad Chabanne

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural templa

  17. Lightweight enterprise architectures

    CERN Document Server

    Theuerkorn, Fenix

    2004-01-01

    STATE OF ARCHITECTUREArchitectural ChaosRelation of Technology and Architecture The Many Faces of Architecture The Scope of Enterprise Architecture The Need for Enterprise ArchitectureThe History of Architecture The Current Environment Standardization Barriers The Need for Lightweight Architecture in the EnterpriseThe Cost of TechnologyThe Benefits of Enterprise Architecture The Domains of Architecture The Gap between Business and ITWhere Does LEA Fit? LEA's FrameworkFrameworks, Methodologies, and Approaches The Framework of LEATypes of Methodologies Types of ApproachesActual System Environmen

  18. Software architecture 1

    CERN Document Server

    Oussalah , Mourad Chabane

    2014-01-01

    Over the past 20 years, software architectures have significantly contributed to the development of complex and distributed systems. Nowadays, it is recognized that one of the critical problems in the design and development of any complex software system is its architecture, i.e. the organization of its architectural elements. Software Architecture presents the software architecture paradigms based on objects, components, services and models, as well as the various architectural techniques and methods, the analysis of architectural qualities, models of representation of architectural template

  19. Chromatin-bound MDM2, a new player in metabolism.

    Science.gov (United States)

    Riscal, Romain; Le Cam, Laurent; Linares, Laetitia K

    2016-01-01

    The oncoprotein MDM2 is recognized as a major negative regulator of the p53 tumor suppressor but growing evidence indicates that its oncogenic activities extend beyond p53. We show that MDM2 is recruited to chromatin independently of p53 to regulate a transcriptional program implicated in amino acid metabolism and redox homeostasis.

  20. Chromatin-bound RNA and the neurobiology of psychiatric disease.

    Science.gov (United States)

    Tushir, J S; Akbarian, S

    2014-04-04

    A large, and still rapidly expanding literature on epigenetic regulation in the nervous system has provided fundamental insights into the dynamic regulation of DNA methylation and post-translational histone modifications in the context of neuronal plasticity in health and disease. Remarkably, however, very little is known about the potential role of chromatin-bound RNAs, including many long non-coding transcripts and various types of small RNAs. Here, we provide an overview on RNA-mediated regulation of chromatin structure and function, with focus on histone lysine methylation and psychiatric disease. Examples of recently discovered chromatin-bound long non-coding RNAs important for neuronal health and function include the brain-derived neurotrophic factor antisense transcript (Bdnf-AS) which regulates expression of the corresponding sense transcript, and LOC389023 which is associated with human-specific histone methylation signatures at the chromosome 2q14.1 neurodevelopmental risk locus by regulating expression of DPP10, an auxillary subunit for voltage-gated K(+) channels. We predict that the exploration of chromatin-bound RNA will significantly advance our current knowledge base in neuroepigenetics and biological psychiatry. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Regulation of chromatin structure by poly(ADP-ribosylation

    Directory of Open Access Journals (Sweden)

    Sascha eBeneke

    2012-09-01

    Full Text Available The interaction of DNA with proteins in the context of chromatin has to be tightly regulated to achieve so different tasks as packaging, transcription, replication and repair. The very rapid and transient post-translational modification of proteins by poly(ADP-ribose has been shown to take part in all four. Originally identified as immediate cellular answer to a variety of genotoxic stresses, already early data indicated the ability of this highly charged nucleic acid-like polymer to modulate nucleosome structure, the basic unit of chromatin. At the same time the enzyme responsible for synthesizing poly(ADP-ribose, the zinc-finger protein poly(ADP-ribose polymerase-1 (PARP1, was shown to control transcription initiation as basic factor TFIIC within the RNA-polymerase II machinery. Later research focused more on PARP-mediated regulation of DNA repair and cell death, but in the last few years, transcription as well as chromatin modulation has re-appeared on the scene. This review will discuss the impact of PARP1 on transcription and transcription factors, its implication in chromatin remodeling for DNA repair and probably also replication, and its role in controlling epigenetic events such as DNA methylation and the functionality of the insulator protein CCCTC-binding factor.

  2. SAGA, TFIID and regulation of transcription through chromatin

    NARCIS (Netherlands)

    Schram, A.W.

    2013-01-01

    Chromatin has an important role in eukaryotic transcription. Research into this role is ongoing and genome-wide analysis has correlated various histone modifications to multiple elements in active and silent genes, such as enhancers, promoters and coding regions. Modifications often serve to recruit

  3. Interaction of maize chromatin-associated HMG proteins with mononucleosomes

    DEFF Research Database (Denmark)

    Lichota, J.; Grasser, Klaus D.

    2003-01-01

    maize HMGA and five different HMGB proteins with mononucleosomes (containing approx. 165 bp of DNA) purified from micrococcal nuclease-digested maize chromatin. The HMGB proteins interacted with the nucleosomes independent of the presence of the linker histone H1, while the binding of HMGA...

  4. Role of chromatin factors in Arabidopsis root stem cell maintenance

    NARCIS (Netherlands)

    Kornet, N.G.

    2008-01-01

    Stem cells replenish the cells present in an organism throughout its lifetime and sustain growth. They have unique characteristics: the capability to self-renew and the potential to differentiate into several cell types. Recently, it has become clear that chromatin factors support these unique

  5. Control of trichome branching by Chromatin Assembly Factor-1

    Directory of Open Access Journals (Sweden)

    Hennig Lars

    2008-05-01

    Full Text Available Abstract Background Chromatin dynamics and stability are both required to control normal development of multicellular organisms. Chromatin assembly factor CAF-1 is a histone chaperone that facilitates chromatin formation and the maintenance of specific chromatin states. In plants and animals CAF-1 is essential for normal development, but it is poorly understood which developmental pathways require CAF-1 function. Results Mutations in all three CAF-1 subunits affect Arabidopsis trichome morphology and lack of CAF-1 function results in formation of trichomes with supernumerary branches. This phenotype can be partially alleviated by external sucrose. In contrast, other aspects of the CAF-1 mutant phenotype, such as defective meristem function and organ formation, are aggravated by external sucrose. Double mutant analyses revealed epistatic interactions between CAF-1 mutants and stichel, but non-epistatic interactions between CAF-1 mutants and glabra3 and kaktus. In addition, mutations in CAF-1 could partly suppress the strong overbranching and polyploidization phenotype of kaktus mutants. Conclusion CAF-1 is required for cell differentiation and regulates trichome development together with STICHEL in an endoreduplication-independent pathway. This function of CAF-1 can be partially substituted by application of exogenous sucrose. Finally, CAF-1 is also needed for the high degree of endoreduplication in kaktus mutants and thus for the realization of kaktus' extreme overbranching phenotype.

  6. Trichostatin A induced histone acetylation causes decondensation of interphase chromatin.

    NARCIS (Netherlands)

    T.A. Knoch (Tobias); M. Wachsmuth (Malte); M. Frank-Stöhr (Monika); M. Stöhr (Michael); C.P. Bacher (Christian); K. Rippe (Karsten)

    2004-01-01

    textabstractThe effect of trichostatin A (TSA)-induced histone acetylation on the interphase chromatin structure was visualized in vivo with a HeLa cell line stably expressing histone H2A, which was fused to enhanced yellow fluorescent protein. The globally increased histone acetylation caused a

  7. Epigenetic regulation and chromatin remodeling in learning and memory.

    Science.gov (United States)

    Kim, Somi; Kaang, Bong-Kiun

    2017-01-13

    Understanding the underlying mechanisms of memory formation and maintenance has been a major goal in the field of neuroscience. Memory formation and maintenance are tightly controlled complex processes. Among the various processes occurring at different levels, gene expression regulation is especially crucial for proper memory processing, as some genes need to be activated while some genes must be suppressed. Epigenetic regulation of the genome involves processes such as DNA methylation and histone post-translational modifications. These processes edit genomic properties or the interactions between the genome and histone cores. They then induce structural changes in the chromatin and lead to transcriptional changes of different genes. Recent studies have focused on the concept of chromatin remodeling, which consists of 3D structural changes in chromatin in relation to gene regulation, and is an important process in learning and memory. In this review, we will introduce three major epigenetic processes involved in memory regulation: DNA methylation, histone methylation and histone acetylation. We will also discuss general mechanisms of long-term memory storage and relate the epigenetic control of learning and memory to chromatin remodeling. Finally, we will discuss how epigenetic mechanisms can contribute to the pathologies of neurological disorders and cause memory-related symptoms.

  8. Effect of triiodothyronine on rat liver chromatin protein kinase

    International Nuclear Information System (INIS)

    Kruh, J.; Tichonicky, L.

    1976-01-01

    1) Injection of triiodothyronine to rats stimulates protein kinase activity in liver chromatin nonhistone proteins. A significant increase was found after two daily injections. A 4-fold increase was observed with the purified enzyme after eight daily injections of the hormone. No variations were observed in cytosol protein kinase activity. Electrophoretic pattern, effect of heat denaturation, effect of p-hydroxymercuribenzoate seem to indicate that the enzyme present in treated rats is not identical to the enzyme in control animals, which suggests that thyroid hormone has induced nuclear protein kinase. Diiodothyronine, 3, 3', 5'-triiodothyronine have no effect on protein kinase. 2) Chromatin non-histone proteins isolated from rats injected with triiodothyronine incorporated more 32 P when incubated with [γ- 32 P]ATP than the chromatin proteins from untreated rats. Thyroidectomy reduced the in vitro 32 P incorporation. It is suggested that some of the biological activity of thyroid hormone could be mediated through its effect on chromatin non-histone proteins. (orig.) [de

  9. PREDICTION OF CHROMATIN STATES USING DNA SEQUENCE PROPERTIES

    KAUST Repository

    Bahabri, Rihab R.

    2013-01-01

    to a particular chromatin state. Of four classification algorithms (C4.5, Naive Bayes, Random Forest, and SVM) used for this purpose, the decision tree based classifiers (C4.5 and Random Forest) yielded best results among those we evaluated. Our results

  10. Chromatin-regulating proteins as targets for cancer therapy

    International Nuclear Information System (INIS)

    Oike, Takahiro; Ogiwara, Hideaki; Kohno, Takashi; Amornwichet, Napapat; Nakano, Takashi

    2014-01-01

    Chromatin-regulating proteins represent a large class of novel targets for cancer therapy. In the context of radiotherapy, acetylation and deacetylation of histones by histone acetyltransferases (HATs) and histone deacetylases (HDACs) play important roles in the repair of DNA double-strand breaks generated by ionizing irradiation, and are therefore attractive targets for radiosensitization. Small-molecule inhibitors of HATs (garcinol, anacardic acid and curcumin) and HDACs (vorinostat, sodium butyrate and valproic acid) have been shown to sensitize cancer cells to ionizing irradiation in preclinical models, and some of these molecules are being tested in clinical trials, either alone or in combination with radiotherapy. Meanwhile, recent large-scale genome analyses have identified frequent mutations in genes encoding chromatin-regulating proteins, especially in those encoding subunits of the SWI/SNF chromatin-remodeling complex, in various human cancers. These observations have driven researchers toward development of targeted therapies against cancers carrying these mutations. DOT1L inhibition in MLL-rearranged leukemia, EZH2 inhibition in EZH2-mutant or MLL-rearranged hematologic malignancies and SNF5-deficient tumors, BRD4 inhibition in various hematologic malignancies, and BRM inhibition in BRG1-deficient tumors have demonstrated promising anti-tumor effects in preclinical models, and these strategies are currently awaiting clinical application. Overall, the data collected so far suggest that targeting chromatin-regulating proteins is a promising strategy for tomorrow's cancer therapy, including radiotherapy and molecularly targeted chemotherapy. (author)

  11. Connecting the dots: chromatin and alternative splicing in EMT.

    Science.gov (United States)

    Warns, Jessica A; Davie, James R; Dhasarathy, Archana

    2016-02-01

    Nature has devised sophisticated cellular machinery to process mRNA transcripts produced by RNA Polymerase II, removing intronic regions and connecting exons together, to produce mature RNAs. This process, known as splicing, is very closely linked to transcription. Alternative splicing, or the ability to produce different combinations of exons that are spliced together from the same genomic template, is a fundamental means of regulating protein complexity. Similar to transcription, both constitutive and alternative splicing can be regulated by chromatin and its associated factors in response to various signal transduction pathways activated by external stimuli. This regulation can vary between different cell types, and interference with these pathways can lead to changes in splicing, often resulting in aberrant cellular states and disease. The epithelial to mesenchymal transition (EMT), which leads to cancer metastasis, is influenced by alternative splicing events of chromatin remodelers and epigenetic factors such as DNA methylation and non-coding RNAs. In this review, we will discuss the role of epigenetic factors including chromatin, chromatin remodelers, DNA methyltransferases, and microRNAs in the context of alternative splicing, and discuss their potential involvement in alternative splicing during the EMT process.

  12. Modulation of the Chromatin Phosphoproteome by the Haspin Protein Kinase

    DEFF Research Database (Denmark)

    Maiolica, Alessio; de Medina-Redondo, Maria; Schoof, Erwin

    2014-01-01

    , histone H3 is the only confirmed Haspin substrate. We used a combination of biochemical, pharmacological, and mass spectrometric approaches to study the consequences of Haspin inhibition in mitotic cells. We quantified 3964 phosphorylation sites on chromatin- associated proteins and identified a Haspin...

  13. Chromatin Structure in Cell Differentiation, Aging and Cancer

    NARCIS (Netherlands)

    S. Kheradmand Kia (Sima)

    2009-01-01

    textabstractChromatin is the structure that the eukaryotic genome is packaged into, allowing over a metre of DNA to fit into the small volume of the nucleus. It is composed of DNA and proteins, most of which are histones. This DNA-protein complex is the template for a number of essential cell

  14. Local chromatin structure of heterochromatin regulates repeated DNA stability, nucleolus structure, and genome integrity

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jamy C. [Univ. of California, Berkeley, CA (United States)

    2007-01-01

    Heterochromatin constitutes a significant portion of the genome in higher eukaryotes; approximately 30% in Drosophila and human. Heterochromatin contains a high repeat DNA content and a low density of protein-encoding genes. In contrast, euchromatin is composed mostly of unique sequences and contains the majority of single-copy genes. Genetic and cytological studies demonstrated that heterochromatin exhibits regulatory roles in chromosome organization, centromere function and telomere protection. As an epigenetically regulated structure, heterochromatin formation is not defined by any DNA sequence consensus. Heterochromatin is characterized by its association with nucleosomes containing methylated-lysine 9 of histone H3 (H3K9me), heterochromatin protein 1 (HP1) that binds H3K9me, and Su(var)3-9, which methylates H3K9 and binds HP1. Heterochromatin formation and functions are influenced by HP1, Su(var)3-9, and the RNA interference (RNAi) pathway. My thesis project investigates how heterochromatin formation and function impact nuclear architecture, repeated DNA organization, and genome stability in Drosophila melanogaster. H3K9me-based chromatin reduces extrachromosomal DNA formation; most likely by restricting the access of repair machineries to repeated DNAs. Reducing extrachromosomal ribosomal DNA stabilizes rDNA repeats and the nucleolus structure. H3K9me-based chromatin also inhibits DNA damage in heterochromatin. Cells with compromised heterochromatin structure, due to Su(var)3-9 or dcr-2 (a component of the RNAi pathway) mutations, display severe DNA damage in heterochromatin compared to wild type. In these mutant cells, accumulated DNA damage leads to chromosomal defects such as translocations, defective DNA repair response, and activation of the G2-M DNA repair and mitotic checkpoints that ensure cellular and animal viability. My thesis research suggests that DNA replication, repair, and recombination mechanisms in heterochromatin differ from those in

  15. Architectural design decisions

    NARCIS (Netherlands)

    Jansen, Antonius Gradus Johannes

    2008-01-01

    A software architecture can be considered as the collection of key decisions concerning the design of the software of a system. Knowledge about this design, i.e. architectural knowledge, is key for understanding a software architecture and thus the software itself. Architectural knowledge is mostly

  16. Information Integration Architecture Development

    OpenAIRE

    Faulkner, Stéphane; Kolp, Manuel; Nguyen, Duy Thai; Coyette, Adrien; Do, Thanh Tung; 16th International Conference on Software Engineering and Knowledge Engineering

    2004-01-01

    Multi-Agent Systems (MAS) architectures are gaining popularity for building open, distributed, and evolving software required by systems such as information integration applications. Unfortunately, despite considerable work in software architecture during the last decade, few research efforts have aimed at truly defining patterns and languages for designing such multiagent architectures. We propose a modern approach based on organizational structures and architectural description lan...

  17. Fragments of Architecture

    DEFF Research Database (Denmark)

    Bang, Jacob Sebastian

    2016-01-01

    Topic 3: “Case studies dealing with the artistic and architectural work of architects worldwide, and the ties between specific artistic and architectural projects, methodologies and products”......Topic 3: “Case studies dealing with the artistic and architectural work of architects worldwide, and the ties between specific artistic and architectural projects, methodologies and products”...

  18. Widespread Chromatin Accessibility at Repetitive Elements Links Stem Cells with Human Cancer

    Directory of Open Access Journals (Sweden)

    Nicholas C. Gomez

    2016-11-01

    Full Text Available Chromatin regulation is critical for differentiation and disease. However, features linking the chromatin environment of stem cells with disease remain largely unknown. We explored chromatin accessibility in embryonic and multipotent stem cells and unexpectedly identified widespread chromatin accessibility at repetitive elements. Integrating genomic and biochemical approaches, we demonstrate that these sites of increased accessibility are associated with well-positioned nucleosomes marked by distinct histone modifications. Differentiation is accompanied by chromatin remodeling at repetitive elements associated with altered expression of genes in relevant developmental pathways. Remarkably, we found that the chromatin environment of Ewing sarcoma, a mesenchymally derived tumor, is shared with primary mesenchymal stem cells (MSCs. Accessibility at repetitive elements in MSCs offers a permissive environment that is exploited by the critical oncogene responsible for this cancer. Our data demonstrate that stem cells harbor a unique chromatin landscape characterized by accessibility at repetitive elements, a feature associated with differentiation and oncogenesis.

  19. 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells.

    Directory of Open Access Journals (Sweden)

    Krzysztof Poterlowicz

    2017-09-01

    Full Text Available Mammalian genomes contain several dozens of large (>0.5 Mbp lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene

  20. Neutron scatter studies of chromatin structures related to functions

    International Nuclear Information System (INIS)

    Bradbury, E.M.

    1992-01-01

    Despite of setbacks in the lack of neutrons for the proposed We have made considerable progress in chromatin reconstitution with the VLR histone H1/H5 and in understanding the dynamics of nucleosomes. A ferromagnetic fluid was developed to align biological molecules for structural studies using small-angle-neutron-scattering. We have also identified and characterized an intrinsically bent DNA region flanking the RNA polymerase I binding site of the ribosomal RNA gene in Physarum Polycephalum. Finally projects in progress are in the areas of studying the interatctions of histone H4 amino-terminus peptide 1-23 and acetylated 1-23 peptide with DNA using thermal denaturation; study of GGAAT repeats found in human centromeres using high resolution Nuclear magnetic Resonance and nuclease sentivity assay; and the role of histones and other sperm specific proteins with sperm chromatin

  1. Neutron scatter studies of chromatin structures related to functions

    International Nuclear Information System (INIS)

    Bradbury, E.M.

    1992-01-01

    We have made considerable progress in chromatin reconstitution with very lysine rich histone H1/H5 and in understanding the dynamics of nucleosomes. A ferromagnetic fluid was developed to align biological molecules for structural studies using small-angle-neutron-scattering. We have also identified and characterized in intrinsically bent DNA region flaking the RNA polymerase I binding site of the ribosomal RNA gene in Physarum Polycephalum. Finally projects in progress are in the areas of studying the interactions of histone H4 amino-terminus peptide 1-23 and acetylated 1-23 peptide with DNA using thermal denaturation; study of GGAAT repeats found in human centromeres using high resolution Nuclear Magnetic Resonance and nuclease sentivity assay; and the role of histones and other sperm specific proteins with sperm chromatin

  2. Atomic force microscopy on chromosomes, chromatin and DNA: a review.

    Science.gov (United States)

    Kalle, Wouter; Strappe, Padraig

    2012-12-01

    The purpose of this review is to discuss the achievements and progress that has been made in the use of atomic force microscopy in DNA related research in the last 25 years. For this review DNA related research is split up in chromosomal-, chromatin- and DNA focused research to achieve a logical flow from large- to smaller structures. The focus of this review is not only on the AFM as imaging tool but also on the AFM as measuring tool using force spectroscopy, as therein lays its greatest advantage and future. The amazing technological and experimental progress that has been made during the last 25 years is too extensive to fully cover in this review but some key developments and experiments have been described to give an overview of the evolution of AFM use from 'imaging tool' to 'measurement tool' on chromosomes, chromatin and DNA. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

  3. Encounter times of chromatin loci influenced by polymer decondensation

    Science.gov (United States)

    Amitai, A.; Holcman, D.

    2018-03-01

    The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude. We derive here new asymptotic formula for the MFET, confirmed by Brownian simulations. We conclude from the present modeling approach that the fast search for homology is mediated by a local chromatin decondensation due to the release of multiple chromatin tethering forces. The present scenario could explain how the homologous recombination pathway for double-stranded DNA repair is controlled by its random search step.

  4. Histone occurrence in chromatin from Peridinium balticum, a binucleate dinoflagellate.

    Science.gov (United States)

    Rizzo, P J; Cox, E R

    1977-12-23

    Peridinium balticum is one of two dinoflagellates known to have dissimilar nuclei together in the same cell. One nucleus (dinokaryotic) has permanently condensed chromosomes, while the other (eukaryotic) does not have morphologically distinct chromosomes. Acid extracts of chromatin prepared from a mixture of dinokaryotic and eukaryotic nuclei and purified eukaryotic nuclei give four bands that co-migrate with four of the five histones from calf thymus when analyzed in urea-containing polyacrylamide gels.

  5. Circular chromatin complexes in human lymphocytes high-resolution autoradiography

    International Nuclear Information System (INIS)

    Becak, M.L.; Fukuda-Pizzocaro, K.; Santos, R. de C.S. dos; Brunner, O.

    1985-01-01

    Transcriptionally active chromatin fibers were observed in chromosomes presenting the loops/scaffold configuration. The active fibers showed altered nucleosomes and presented multiforked aspects which led to the formation of ring complexes. The ribonucleoprotein transcripts (RNP) appeared as networks of 0.1 μm or multiples tandemly disposed along the fiber. It is suggested that the ring complexes belong to the human genome. The possibility that these circular structures come from a prokaryote is also considered. (author) [pt

  6. Light scattering measurements supporting helical structures for chromatin in solution.

    Science.gov (United States)

    Campbell, A M; Cotter, R I; Pardon, J F

    1978-05-01

    Laser light scattering measurements have been made on a series of polynucleosomes containing from 50 to 150 nucleosomes. Radii of gyration have been determined as a function of polynucleosome length for different ionic strength solutions. The results suggest that at low ionic strength the chromatin adopts a loosely helical structure rather than a random coil. The helix becomes more regular on increasing the ionic strength, the dimension resembling those proposed by Finch and Klug for their solenoid model.

  7. ATM and KAT5 safeguard replicating chromatin against formaldehyde damage

    Science.gov (United States)

    Ortega-Atienza, Sara; Wong, Victor C.; DeLoughery, Zachary; Luczak, Michal W.; Zhitkovich, Anatoly

    2016-01-01

    Many carcinogens damage both DNA and protein constituents of chromatin, and it is unclear how cells respond to this compound injury. We examined activation of the main DNA damage-responsive kinase ATM and formation of DNA double-strand breaks (DSB) by formaldehyde (FA) that forms histone adducts and replication-blocking DNA-protein crosslinks (DPC). We found that low FA doses caused a strong and rapid activation of ATM signaling in human cells, which was ATR-independent and restricted to S-phase. High FA doses inactivated ATM via its covalent dimerization and formation of larger crosslinks. FA-induced ATM signaling showed higher CHK2 phosphorylation but much lower phospho-KAP1 relative to DSB inducers. Replication blockage by DPC did not produce damaged forks or detectable amounts of DSB during the main wave of ATM activation, which did not require MRE11. Chromatin-monitoring KAT5 (Tip60) acetyltransferase was responsible for acetylation and activation of ATM by FA. KAT5 and ATM were equally important for triggering of intra-S-phase checkpoint and ATM signaling promoted recovery of normal human cells after low-dose FA. Our results revealed a major role of the KAT5-ATM axis in protection of replicating chromatin against damage by the endogenous carcinogen FA. PMID:26420831

  8. [Neutron scatter studies of chromatin structure related to function

    International Nuclear Information System (INIS)

    Bradbury, E.M.

    1990-01-01

    This study is concerned with the application of neutron scatter techniques to the different structural states of nucleosomes and chromatin with the long term objective of understanding how the enormous lengths of DNA are folded into chromosomes. Micrococcal nuclease digestion kinetics have defined two subnucleosome particles; the chromatosome with 168 bp DNA, the histone octamer and one H1 and the nucleosome core particle with 146 bp DNA and the histone octamer. As will be discussed, the structure of the 146 bp DNA core particle is known in solution at low resolution from neutron scatter studies and in crystals. Based on this structure, the authors have a working model for the chromatosome and the mode of binding of H1. In order to define the structure of the nucleosome and also the different orders of chromatin structures they need to know the paths of DNA that link nucleosomes and the factors associated with chromosome functions that act on those DNA paths. The major region for this situation is the inherent variabilities in nucleosome DNA sequences, in the histone subtypes and their states of chemical modification and in the precise locations of nucleosomes. Such variabilities obscure the underlying principles that govern the packaging of DNA into the different structural states of nucleosomes and chromatin. The only way to elucidate these principles is to study the structures of nucleosomes and oligonucleosomes that are fully defined. They have largely achieved these objectives

  9. The protein encoded by the proto-oncogene DEK changes the topology of chromatin and reduces the efficiency of DNA replication in a chromatin-specific manner

    DEFF Research Database (Denmark)

    Alexiadis, V; Waldmann, T; Andersen, Jens S.

    2000-01-01

    The structure of chromatin regulates the genetic activity of the underlying DNA sequence. We report here that the protein encoded by the proto-oncogene DEK, which is involved in acute myelogenous leukemia, induces alterations of the superhelical density of DNA in chromatin. The change in topology...

  10. Sustained activation of STAT5 is essential for chromatin remodeling and maintenance of mammary-specific function

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Ren; Nelson, Celeste M.; Muschler, John L.; Veiseh, Mandana; Vonderhaar, Barbara K.; Bissell, Mina J.

    2009-06-03

    Epithelial cells, once dissociated and placed in two-dimensional (2D) cultures, rapidly lose tissue-specific functions. We showed previously that in addition to prolactin, signaling by laminin-111 was necessary to restore functional differentiation of mammary epithelia. Here, we elucidate two additional aspects of laminin-111 action. We show that in 2D cultures, the prolactin receptor is basolaterally localized and physically segregated from its apically placed ligand. Detachment of the cells exposes the receptor to ligation by prolactin leading to signal transducers and activators of transcription protein 5 (STAT5) activation, but only transiently and not sufficiently for induction of milk protein expression. We show that laminin-111 reorganizes mammary cells into polarized acini, allowing both the exposure of the prolactin receptor and sustained activation of STAT5. The use of constitutively active STAT5 constructs showed that the latter is necessary and sufficient for chromatin reorganization and {beta}-casein transcription. These results underscore the crucial role of continuous laminin signaling and polarized tissue architecture in maintenance of transcription factor activation, chromatin organization, and tissue-specific gene expression.

  11. Quantitative FLIM-FRET Microscopy to Monitor Nanoscale Chromatin Compaction In Vivo Reveals Structural Roles of Condensin Complexes

    Directory of Open Access Journals (Sweden)

    David Llères

    2017-02-01

    Full Text Available How metazoan genomes are structured at the nanoscale in living cells and tissues remains unknown. Here, we adapted a quantitative FRET (Förster resonance energy transfer-based fluorescence lifetime imaging microscopy (FLIM approach to assay nanoscale chromatin compaction in living organisms. Caenorhabditis elegans was chosen as a model system. By measuring FRET between histone-tagged fluorescent proteins, we visualized distinct chromosomal regions and quantified the different levels of nanoscale compaction in meiotic cells. Using RNAi and repetitive extrachromosomal array approaches, we defined the heterochromatin state and showed that its architecture presents a nanoscale-compacted organization controlled by Heterochromatin Protein-1 (HP1 and SETDB1 H3-lysine-9 methyltransferase homologs in vivo. Next, we functionally explored condensin complexes. We found that condensin I and condensin II are essential for heterochromatin compaction and that condensin I additionally controls lowly compacted regions. Our data show that, in living animals, nanoscale chromatin compaction is controlled not only by histone modifiers and readers but also by condensin complexes.

  12. Modeling Architectural Patterns’ Behavior Using Architectural Primitives

    NARCIS (Netherlands)

    Waqas Kamal, Ahmad; Avgeriou, Paris

    2008-01-01

    Architectural patterns have an impact on both the structure and the behavior of a system at the architecture design level. However, it is challenging to model patterns’ behavior in a systematic way because modeling languages do not provide the appropriate abstractions and because each pattern

  13. Chromatin organisation and cancer prognosis: a pan-cancer study.

    Science.gov (United States)

    Kleppe, Andreas; Albregtsen, Fritz; Vlatkovic, Ljiljana; Pradhan, Manohar; Nielsen, Birgitte; Hveem, Tarjei S; Askautrud, Hanne A; Kristensen, Gunnar B; Nesbakken, Arild; Trovik, Jone; Wæhre, Håkon; Tomlinson, Ian; Shepherd, Neil A; Novelli, Marco; Kerr, David J; Danielsen, Håvard E

    2018-03-01

    Chromatin organisation affects gene expression and regional mutation frequencies and contributes to carcinogenesis. Aberrant organisation of DNA has been correlated with cancer prognosis in analyses of the chromatin component of tumour cell nuclei using image texture analysis. As yet, the methodology has not been sufficiently validated to permit its clinical application. We aimed to define and validate a novel prognostic biomarker for the automatic detection of heterogeneous chromatin organisation. Machine learning algorithms analysed the chromatin organisation in 461 000 images of tumour cell nuclei stained for DNA from 390 patients (discovery cohort) treated for stage I or II colorectal cancer at the Aker University Hospital (Oslo, Norway). The resulting marker of chromatin heterogeneity, termed Nucleotyping, was subsequently independently validated in six patient cohorts: 442 patients with stage I or II colorectal cancer in the Gloucester Colorectal Cancer Study (UK); 391 patients with stage II colorectal cancer in the QUASAR 2 trial; 246 patients with stage I ovarian carcinoma; 354 patients with uterine sarcoma; 307 patients with prostate carcinoma; and 791 patients with endometrial carcinoma. The primary outcome was cancer-specific survival. In all patient cohorts, patients with chromatin heterogeneous tumours had worse cancer-specific survival than patients with chromatin homogeneous tumours (univariable analysis hazard ratio [HR] 1·7, 95% CI 1·2-2·5, in the discovery cohort; 1·8, 1·0-3·0, in the Gloucester validation cohort; 2·2, 1·1-4·5, in the QUASAR 2 validation cohort; 3·1, 1·9-5·0, in the ovarian carcinoma cohort; 2·5, 1·8-3·4, in the uterine sarcoma cohort; 2·3, 1·2-4·6, in the prostate carcinoma cohort; and 4·3, 2·8-6·8, in the endometrial carcinoma cohort). After adjusting for established prognostic patient characteristics in multivariable analyses, Nucleotyping was prognostic in all cohorts except for the prostate carcinoma

  14. RNA is an integral component of chromatin that contributes to its structural organization.

    Directory of Open Access Journals (Sweden)

    Antonio Rodríguez-Campos

    Full Text Available Chromatin structure is influenced by multiples factors, such as pH, temperature, nature and concentration of counterions, post-translational modifications of histones and binding of structural non-histone proteins. RNA is also known to contribute to the regulation of chromatin structure as chromatin-induced gene silencing was shown to depend on the RNAi machinery in S. pombe, plants and Drosophila. Moreover, both in Drosophila and mammals, dosage compensation requires the contribution of specific non-coding RNAs. However, whether RNA itself plays a direct structural role in chromatin is not known. Here, we report results that indicate a general structural role for RNA in eukaryotic chromatin. RNA is found associated to purified chromatin prepared from chicken liver, or cultured Drosophila S2 cells, and treatment with RNase A alters the structural properties of chromatin. Our results indicate that chromatin-associated RNAs, which account for 2%-5% of total chromatin-associated nucleic acids, are polyA(- and show a size similar to that of the DNA contained in the corresponding chromatin fragments. Chromatin-associated RNA(s are not likely to correspond to nascent transcripts as they are also found bound to chromatin when cells are treated with alpha-amanitin. After treatment with RNase A, chromatin fragments of molecular weight >3.000 bp of DNA showed reduced sedimentation through sucrose gradients and increased sensitivity to micrococcal nuclease digestion. This structural transition, which is observed both at euchromatic and heterochromatic regions, proceeds without loss of histone H1 or any significant change in core-histone composition and integrity.

  15. Evolutionary dynamics of 3D genome architecture following polyploidization in cotton.

    Science.gov (United States)

    Wang, Maojun; Wang, Pengcheng; Lin, Min; Ye, Zhengxiu; Li, Guoliang; Tu, Lili; Shen, Chao; Li, Jianying; Yang, Qingyong; Zhang, Xianlong

    2018-02-01

    The formation of polyploids significantly increases the complexity of transcriptional regulation, which is expected to be reflected in sophisticated higher-order chromatin structures. However, knowledge of three-dimensional (3D) genome structure and its dynamics during polyploidization remains poor. Here, we characterize 3D genome architectures for diploid and tetraploid cotton, and find the existence of A/B compartments and topologically associated domains (TADs). By comparing each subgenome in tetraploids with its extant diploid progenitor, we find that genome allopolyploidization has contributed to the switching of A/B compartments and the reorganization of TADs in both subgenomes. We also show that the formation of TAD boundaries during polyploidization preferentially occurs in open chromatin, coinciding with the deposition of active chromatin modification. Furthermore, analysis of inter-subgenomic chromatin interactions has revealed the spatial proximity of homoeologous genes, possibly associated with their coordinated expression. This study advances our understanding of chromatin organization in plants and sheds new light on the relationship between 3D genome evolution and transcriptional regulation.

  16. In the loop: how chromatin topology links genome structure to function in mechanisms underlying learning and memory.

    Science.gov (United States)

    Watson, L Ashley; Tsai, Li-Huei

    2017-04-01

    Different aspects of learning, memory, and cognition are regulated by epigenetic mechanisms such as covalent DNA modifications and histone post-translational modifications. More recently, the modulation of chromatin architecture and nuclear organization is emerging as a key factor in dynamic transcriptional regulation of the post-mitotic neuron. For instance, neuronal activity induces relocalization of gene loci to 'transcription factories', and specific enhancer-promoter looping contacts allow for precise transcriptional regulation. Moreover, neuronal activity-dependent DNA double-strand break formation in the promoter of immediate early genes appears to overcome topological constraints on transcription. Together, these findings point to a critical role for genome topology in integrating dynamic environmental signals to define precise spatiotemporal gene expression programs supporting cognitive processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Religious architecture: anthropological perspectives

    NARCIS (Netherlands)

    Verkaaik, O.

    2013-01-01

    Religious Architecture: Anthropological Perspectives develops an anthropological perspective on modern religious architecture, including mosques, churches and synagogues. Borrowing from a range of theoretical perspectives on space-making and material religion, this volume looks at how religious

  18. Avionics Architecture for Exploration

    Data.gov (United States)

    National Aeronautics and Space Administration — The goal of the AES Avionics Architectures for Exploration (AAE) project is to develop a reference architecture that is based on standards and that can be scaled and...

  19. RATS: Reactive Architectures

    National Research Council Canada - National Science Library

    Christensen, Marc

    2004-01-01

    This project had two goals: To build an emulation prototype board for a tiled architecture and to demonstrate the utility of a global inter-chip free-space photonic interconnection fabric for polymorphous computer architectures (PCA...

  20. Rhein-Ruhr architecture

    DEFF Research Database (Denmark)

    2002-01-01

    katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider......katalog til udstillingen 'Rhein - Ruhr architecture' Meldahls smedie, 15. marts - 28. april 2002. 99 sider...

  1. Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Hangnoh Lee

    2016-09-01

    Full Text Available Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

  2. Effects of Gene Dose, Chromatin, and Network Topology on Expression in Drosophila melanogaster.

    Science.gov (United States)

    Lee, Hangnoh; Cho, Dong-Yeon; Whitworth, Cale; Eisman, Robert; Phelps, Melissa; Roote, John; Kaufman, Thomas; Cook, Kevin; Russell, Steven; Przytycka, Teresa; Oliver, Brian

    2016-09-01

    Deletions, commonly referred to as deficiencies by Drosophila geneticists, are valuable tools for mapping genes and for genetic pathway discovery via dose-dependent suppressor and enhancer screens. More recently, it has become clear that deviations from normal gene dosage are associated with multiple disorders in a range of species including humans. While we are beginning to understand some of the transcriptional effects brought about by gene dosage changes and the chromosome rearrangement breakpoints associated with them, much of this work relies on isolated examples. We have systematically examined deficiencies of the left arm of chromosome 2 and characterize gene-by-gene dosage responses that vary from collapsed expression through modest partial dosage compensation to full or even over compensation. We found negligible long-range effects of creating novel chromosome domains at deletion breakpoints, suggesting that cases of gene regulation due to altered nuclear architecture are rare. These rare cases include trans de-repression when deficiencies delete chromatin characterized as repressive in other studies. Generally, effects of breakpoints on expression are promoter proximal (~100bp) or in the gene body. Effects of deficiencies genome-wide are in genes with regulatory relationships to genes within the deleted segments, highlighting the subtle expression network defects in these sensitized genetic backgrounds.

  3. Architecture and Film

    OpenAIRE

    Mohammad Javaheri, Saharnaz

    2016-01-01

    Film does not exist without architecture. In every movie that has ever been made throughout history, the cinematic image of architecture is embedded within the picture. Throughout my studies and research, I began to see that there is no director who can consciously or unconsciously deny the use of architectural elements in his or her movies. Architecture offers a strong profile to distinguish characters and story. In the early days, films were shot in streets surrounde...

  4. Elements of Architecture

    DEFF Research Database (Denmark)

    Elements of Architecture explores new ways of engaging architecture in archaeology. It conceives of architecture both as the physical evidence of past societies and as existing beyond the physical environment, considering how people in the past have not just dwelled in buildings but have existed...

  5. Aggregation of fragmented chromatin associated with the appearance of products of its nuclease treatment

    International Nuclear Information System (INIS)

    Lobanenkov, V.V.; Mironov, N.M.; Kupriyanova, E.I.; Shapot, V.S.

    1986-01-01

    Isolated cell nuclei were incubated with nucleases, and then the chromatin was extracted with a low-salt buffer. When degradation of the nuclear chromatin DNase I or micrococcal nuclease is intensified, solubilization of the deoxyribonucleoprotein (DNP) in low-salt buffer at first increases, reaching a maximum in the case of hydrolysis of 2-4% of the nuclear DNA, but after intensive treatment with nucleases, it decreases sharply. Soluble fragmented chromatin is aggregated during treatment with DNase I. The addition of exogenous products of nuclease treatment of isolated nuclei to a preparation of gelatinous chromatin induces its aggregation. Pretreatment of nuclear chromatin with RNase prevents the solubilization of DNP by solutions with low ionic strength. Certain experimental data obtained using rigorous nuclease treatment are discussed; for their interpretation it is necessary to consider the effect of aggregation of fragmented chromatin by products of its nuclease degradation

  6. A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene

    DEFF Research Database (Denmark)

    Singh, Hari R; Nardozza, Aurelio P; Möller, Ingvar R

    2017-01-01

    DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain......-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain's interaction with PARP1 under non-DNA damage conditions. Somatic...... cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD+-metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation....

  7. Restoring chromatin after replication: How new and old histone marks come together

    DEFF Research Database (Denmark)

    Jasencakova, Zusana; Groth, Anja

    2010-01-01

    In dividing cells genome stability and function rely on faithful transmission of both DNA sequence and its organization into chromatin. In the course of DNA replication chromatin undergoes transient genome-wide disruption followed by restoration on new DNA. This involves tight coordination of DNA...... replication and chromatin assembly processes in time and space. Dynamic recycling and de novo deposition of histones are fundamental for chromatin restoration. Histone post-translational modifications (PTMs) are thought to have a causal role in establishing distinct chromatin structures. Here we discuss PTMs...... present on new and parental histones and how they influence genome stability and restoration of epigenetically defined domains. Newly deposited histones must change their signature in the process of chromatin restoration, this may occur in a step-wise fashion involving replication-coupled processes...

  8. Autodigestion of chromatin in some radiosensitive and radioresistant mouse cells. Role of proteolysis and endonucleolysis

    International Nuclear Information System (INIS)

    Suciu, D.; Bojan, O.

    1981-01-01

    Evidence is presented indicating that mouse thymus, spleen, kidney, lung and heart contain a protease activity with relatively high specificity for histones. It is suggested that degradation of chromatin occurring in irradiated lymphoid tissues is produced by the action of alkaline endonuclease in association with this histone protease. The autodigestion of chromatin was assessed by determining the release of soluble chromatin from cells suspended in sucrose media of low ionic strength. It was found that the protease inhibitors, phenylmethylsulphonyl fluoride and especially NaHSO 3 , were also capable of depressing the activity of alkaline endonuclease, the fragmentation of chromatin, and the release of soluble chromatin. The results suggest that the release of histones from irradiated lymphoid tissues cannot be considered as a determinant step in the fragmentation of DNA in chromatin. (author)

  9. Temporal profiling of the chromatin proteome reveals system-wide responses to replication inhibition

    DEFF Research Database (Denmark)

    Khoudoli, Guennadi A; Gillespie, Peter J; Stewart, Graeme

    2008-01-01

    Although the replication, expression, and maintenance of DNA are well-studied processes, the way that they are coordinated is poorly understood. Here, we report an analysis of the changing association of proteins with chromatin (the chromatin proteome) during progression through interphase...... of the cell cycle. Sperm nuclei were incubated in Xenopus egg extracts, and chromatin-associated proteins were analyzed by mass spectrometry at different times. Approximately 75% of the proteins varied in abundance on chromatin by more than 15%, suggesting that the chromatin proteome is highly dynamic....... Proteins were then assigned to one of 12 different clusters on the basis of their pattern of chromatin association. Each cluster contained functional groups of proteins involved in different nuclear processes related to progression through interphase. We also blocked DNA replication by inhibiting either...

  10. DNA repair goes hip-hop: SMARCA and CHD chromatin remodellers join the break dance.

    Science.gov (United States)

    Rother, Magdalena B; van Attikum, Haico

    2017-10-05

    Proper signalling and repair of DNA double-strand breaks (DSB) is critical to prevent genome instability and diseases such as cancer. The packaging of DNA into chromatin, however, has evolved as a mere obstacle to these DSB responses. Posttranslational modifications and ATP-dependent chromatin remodelling help to overcome this barrier by modulating nucleosome structures and allow signalling and repair machineries access to DSBs in chromatin. Here we recap our current knowledge on how ATP-dependent SMARCA- and CHD-type chromatin remodellers alter chromatin structure during the signalling and repair of DSBs and discuss how their dysfunction impacts genome stability and human disease.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Authors.

  11. Vital architecture, slow momentum policy

    DEFF Research Database (Denmark)

    Braae, Ellen Marie

    2010-01-01

    A reflection on the relation between Danish landscape architecture policy and the statements made through current landscape architectural project.......A reflection on the relation between Danish landscape architecture policy and the statements made through current landscape architectural project....

  12. Parvovirus induced alterations in nuclear architecture and dynamics.

    Directory of Open Access Journals (Sweden)

    Teemu O Ihalainen

    2009-06-01

    Full Text Available The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching (FRAP studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analysis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications.

  13. Biochemical and structural characterization of Cren7, a novel chromatin protein conserved among Crenarchaea

    OpenAIRE

    Guo, Li; Feng, Yingang; Zhang, Zhenfeng; Yao, Hongwei; Luo, Yuanming; Wang, Jinfeng; Huang, Li

    2007-01-01

    Archaea contain a variety of chromatin proteins consistent with the evolution of different genome packaging mechanisms. Among the two main kingdoms in the Archaea, Euryarchaeota synthesize histone homologs, whereas Crenarchaeota have not been shown to possess a chromatin protein conserved at the kingdom level. We report the identification of Cren7, a novel family of chromatin proteins highly conserved in the Crenarchaeota. A small, basic, methylated and abundant protein, Cren7 displays a high...

  14. Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0152 TITLE: Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-14-1-0152 Scaffold Attachment Factor B1: A Novel Chromatin Regulator of Prostate Cancer Metabolism... chromatin immunoprecipitation-next generation DNA sequencing (ChIP-seq) and integrative network modeling to identify the SAFB1 cistrome and the extent of

  15. Osmotic stress alters chromatin condensation and nucleocytoplasmic transport

    Energy Technology Data Exchange (ETDEWEB)

    Finan, John D.; Leddy, Holly A. [Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC (United States); Department of Biomedical Engineering, Duke University, Durham, NC (United States); Guilak, Farshid, E-mail: guilak@duke.edu [Department of Orthopaedic Surgery, Duke University Medical Center, Durham, NC (United States); Department of Biomedical Engineering, Duke University, Durham, NC (United States)

    2011-05-06

    Highlights: {yields} The rate of nucleocytoplasmic transport increases under hyper-osmotic stress. {yields} The mechanism is a change in nuclear geometry, not a change in permeability of the nuclear envelope. {yields} Intracytoplasmic but not intranuclear diffusion is sensitive to osmotic stress. {yields} Pores in the chromatin of the nucleus enlarge under hyper-osmotic stress. -- Abstract: Osmotic stress is a potent regulator of biological function in many cell types, but its mechanism of action is only partially understood. In this study, we examined whether changes in extracellular osmolality can alter chromatin condensation and the rate of nucleocytoplasmic transport, as potential mechanisms by which osmotic stress can act. Transport of 10 kDa dextran was measured both within and between the nucleus and the cytoplasm using two different photobleaching methods. A mathematical model was developed to describe fluorescence recovery via nucleocytoplasmic transport. As osmolality increased, the diffusion coefficient of dextran decreased in the cytoplasm, but not the nucleus. Hyper-osmotic stress decreased nuclear size and increased nuclear lacunarity, indicating that while the nucleus was getting smaller, the pores and channels interdigitating the chromatin had expanded. The rate of nucleocytoplasmic transport was increased under hyper-osmotic stress but was insensitive to hypo-osmotic stress, consistent with the nonlinear osmotic properties of the nucleus. The mechanism of this osmotic sensitivity appears to be a change in the size and geometry of the nucleus, resulting in a shorter effective diffusion distance for the nucleus. These results may explain physical mechanisms by which osmotic stress can influence intracellular signaling pathways that rely on nucleocytoplasmic transport.

  16. Chromatin association of UHRF1 during the cell cycle

    KAUST Repository

    Al-Gashgari, Bothayna

    2017-05-01

    Ubiquitin-like with PHD and RING Finger domains 1 (UHRF1) is a nuclear protein that associates with chromatin. Regardless of the various functions of UHRF1 in the cell, one of its more important functions is its role in the maintenance of DNA methylation patterns by the recruitment of DNMT1. Studies on UHRF1 based on this function have revealed the importance of UHRF1 during the cell cycle. Moreover, based on different studies various factors were described to be involved in the regulation of UHRF1 with different functionalities that can control its binding affinity to different targets on chromatin. These factors are regulated differently in a cell cycle specific manner. In light of this, we propose that UHRF1 has different binding behaviors during the cell cycle in regard to its association with chromatin. In this project, we first analyzed the binding behavior of endogenous UHRF1 from different unsynchronized cell systems in pull-down assays with peptides and oligonucleotides. Moreover, to analyze UHRF1 binding behavior during the cell cycle, we used two different approaches. First we sorted Jurkat and HT1080 cells based on their cell cycle stage using FACS analysis. Additionally, we synchronized HeLa cells to different stages of the cell cycle by chemical treatments, and used extracts from cellsorting and cell synchronization experiments for pull-down assays. We observed that UHRF1 in different cell systems has different preferences in regard to its binding to H3 unmodified and H3K9me3. Moreover, we detected that UHRF1, in general, displays different patterns between different stages of cell cycle; however, we cannot draw a final model for UHRF1 binding pattern during cell cycle.

  17. Analysis of Myc-induced histone modifications on target chromatin.

    Directory of Open Access Journals (Sweden)

    Francesca Martinato

    Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

  18. Chromatin structure and epigenetics of tumour cells: A review

    Czech Academy of Sciences Publication Activity Database

    Bártová, Eva; Krejčí, Jana; Hájek, R.; Harničarová, Andrea; Kozubek, Stanislav

    2009-01-01

    Roč. 9, č. 1 (2009), s. 51-61 ISSN 1871-529X R&D Projects: GA AV ČR(CZ) 1QS500040508; GA ČR(CZ) GA204/06/0978 Grant - others:GA MŠk(CZ) LC06027; GA MŠk(CZ) LC535 Program:LC; LC Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : tumour cells * chromatin * radiation Subject RIV: BO - Biophysics

  19. Keeping it quiet: chromatin control of gammaherpesvirus latency.

    Science.gov (United States)

    Lieberman, Paul M

    2013-12-01

    The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) establish long-term latent infections associated with diverse human cancers. Viral oncogenesis depends on the ability of the latent viral genome to persist in host nuclei as episomes that express a restricted yet dynamic pattern of viral genes. Multiple epigenetic events control viral episome generation and maintenance. This Review highlights some of the recent findings on the role of chromatin assembly, histone and DNA modifications, and higher-order chromosome structures that enable gammaherpesviruses to establish stable latent infections that mediate viral pathogenesis.

  20. Quantitative Immunofluorescence Analysis of Nucleolus-Associated Chromatin.

    Science.gov (United States)

    Dillinger, Stefan; Németh, Attila

    2016-01-01

    The nuclear distribution of eu- and heterochromatin is nonrandom, heterogeneous, and dynamic, which is mirrored by specific spatiotemporal arrangements of histone posttranslational modifications (PTMs). Here we describe a semiautomated method for the analysis of histone PTM localization patterns within the mammalian nucleus using confocal laser scanning microscope images of fixed, immunofluorescence stained cells as data source. The ImageJ-based process includes the segmentation of the nucleus, furthermore measurements of total fluorescence intensities, the heterogeneity of the staining, and the frequency of the brightest pixels in the region of interest (ROI). In the presented image analysis pipeline, the perinucleolar chromatin is selected as primary ROI, and the nuclear periphery as secondary ROI.

  1. Genomic and chromatin signals underlying transcription start-site selection

    DEFF Research Database (Denmark)

    Valen, Eivind; Sandelin, Albin Gustav

    2011-01-01

    A central question in cellular biology is how the cell regulates transcription and discerns when and where to initiate it. Locating transcription start sites (TSSs), the signals that specify them, and ultimately elucidating the mechanisms of regulated initiation has therefore been a recurrent theme....... In recent years substantial progress has been made towards this goal, spurred by the possibility of applying genome-wide, sequencing-based analysis. We now have a large collection of high-resolution datasets identifying locations of TSSs, protein-DNA interactions, and chromatin features over whole genomes...

  2. Exporting Humanist Architecture

    DEFF Research Database (Denmark)

    Nielsen, Tom

    2016-01-01

    The article is a chapter in the catalogue for the Danish exhibition at the 2016 Architecture Biennale in Venice. The catalogue is conceived at an independent book exploring the theme Art of Many - The Right to Space. The chapter is an essay in this anthology tracing and discussing the different...... values and ethical stands involved in the export of Danish Architecture. Abstract: Danish architecture has, in a sense, been driven by an unwritten contract between the architects and the democratic state and its institutions. This contract may be viewed as an ethos – an architectural tradition...... with inherent aesthetic and moral values. Today, however, Danish architecture is also an export commodity. That raises questions, which should be debated as openly as possible. What does it mean for architecture and architects to practice in cultures and under political systems that do not use architecture...

  3. Software architecture evolution

    DEFF Research Database (Denmark)

    Barais, Olivier; Le Meur, Anne-Francoise; Duchien, Laurence

    2008-01-01

    Software architectures must frequently evolve to cope with changing requirements, and this evolution often implies integrating new concerns. Unfortunately, when the new concerns are crosscutting, existing architecture description languages provide little or no support for this kind of evolution....... The software architect must modify multiple elements of the architecture manually, which risks introducing inconsistencies. This chapter provides an overview, comparison and detailed treatment of the various state-of-the-art approaches to describing and evolving software architectures. Furthermore, we discuss...... one particular framework named Tran SAT, which addresses the above problems of software architecture evolution. Tran SAT provides a new element in the software architecture descriptions language, called an architectural aspect, for describing new concerns and their integration into an existing...

  4. Nucleolar chromatin organization at different activities of soybean root meristematic cell nucleoli.

    Science.gov (United States)

    Stępiński, Dariusz

    2013-06-01

    Nucleolar chromatin, including nucleolus-associated chromatin as well as active and inactive condensed ribosomal DNA (rDNA) chromatin, derives mostly from secondary constrictions known as nucleolus organizer regions containing rDNA genes on nucleolus-forming chromosomes. This chromatin may occupy different nucleolar positions being in various condensation states which may imply different rDNA transcriptional competence. Sections of nucleoli originating from root meristematic cells of soybean seedlings grown at 25 °C (the control), then subjected to chilling stress (10 °C), and next transferred again to 25 °C (the recovery) were used to measure profile areas occupied by nucleolar condensed chromatin disclosed with sodium hydroxide methylation-acetylation plus uranyl acetate technique. The biggest total area of condensed chromatin was found in the nucleoli of chilled plants, while the smallest was found in those of recovered plants in relation to the amounts of chromatin in the control nucleoli. The condensed nucleolar chromatin, in the form of different-sized and different-shaped clumps, was mainly located in fibrillar centers. One can suppose that changes of condensed rDNA chromatin amounts might be a mechanism controlling the number of transcriptionally active rDNA genes as the nucleoli of plants grown under these experimental conditions show different transcriptional activity and morphology.

  5. Extracellular Matrix-Induced Chromatin Modifications in Normal and Malignant Human Breast Cells

    National Research Council Canada - National Science Library

    Beyec, Johanne

    2002-01-01

    .... The changes in gene expression that occur during differentiation or tumorigenesis are accompanied by characteristics patterns of chromatin reorganization, modulated, in part, through highly regulated...

  6. Comparative aspects of basic chromatin proteins in dinoflagellates.

    Science.gov (United States)

    Rizzo, P J

    1981-01-01

    Previous work on histone-like proteins in dinoflagellates is summarized, together with some new data to give an overview of basic proteins in these algae. The first two dinoflagellates studied were both found to contain one major acid-soluble protein that migrated to the same position in acidic-urea gels. When several other genera were studied however, it became apparent that the histone-like proteins from different dinoflagellates were similar but not identical. In view of the great diversity of living dinoflagellates it is speculated that further differences in dinoflagellate basic chromatin proteins will be revealed. Electrophoretic data from the eukaryotic (endosymbiont) nucleus of Peridinium balticum showed the presence of five major components. It is speculated that two of these proteins represent an H1-like doublet and two others correspond to the highly conserved histones H3 and H4. The fifth component is a new histone that may substitute for H2A and H2B in the nucleosome. Because histones and nucleosomes are present in all higher organisms but completely lacking in procaryotes, studies on basic proteins in dinoflagellates will provides insights into the evolution of histones and eucaryotic chromatin organization.

  7. Chromatin Structure and Radiation-Induced Intrachromosome Exchange

    Science.gov (United States)

    Mangala; Zhang, Ye; Hada, Megumi; Cucinotta, Francis A.; Wu, Honglu

    2011-01-01

    We have recently investigated the location of breaks involved in intrachromosomal type exchange events, using the multicolor banding in situ hybridization (mBAND) technique for human chromosome 3. In human epithelial cells exposed to both low- and high-LET radiations in vitro, intrachromosome exchanges were found to occur preferentially between a break in the 3p21 and one in the 3q11. Exchanges were also observed between a break in 3p21 and one in 3q26, but few exchanges were observed between breaks in 3q11 and 3q26, even though the two regions were on the same arm of the chromosome. To explore the relationships between intrachromosome exchanges and chromatin structure, we used probes that hybridize the three regions of 3p21, 3q11 and 3q26, and measured the distance between two of the three regions in interphase cells. We further analyzed fragile sites on the chromosome that have been identified in various types of cancers. Our results demonstrated that the distribution of breaks involved in radiation-induced intrachromosome aberrations depends upon both the location of fragile sites and the folding of chromatins

  8. The role of proteins and metal ions in the protection of chromatin DNA at fast neutrons action

    International Nuclear Information System (INIS)

    Radu, L.; Preoteasa, V.; Radulescu, I.; Constantinescu, B.

    1997-01-01

    The role of chromatin proteins and of some ions on the fast neutrons actions on chromatin DNA from rat Walker tumors was analysed. The DNA in chromatin is effectively protected against fast neutrons actions by DNA bound proteins and specially by histones, because of the limited accessibility of the condensed chromatin DNA to hydroxyl radicals and of the scavenging of radicals by the chromatin proteins. The ions utilised protect chromatin DNA against the damage produced ed by fast neutrons, through the induction of structural DNA changes with a less accessibility to OH radicals. (authors)

  9. Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin

    Directory of Open Access Journals (Sweden)

    Mora Xavier

    2007-05-01

    Full Text Available Abstract Background Histone H1 is involved in the formation and maintenance of chromatin higher order structure. H1 has multiple isoforms; the subtypes differ in timing of expression, extent of phosphorylation and turnover rate. In vertebrates, the amino acid substitution rates differ among subtypes by almost one order of magnitude, suggesting that each subtype might have acquired a unique function. We have devised a competitive assay to estimate the relative binding affinities of histone H1 mammalian somatic subtypes H1a-e and H1° for long chromatin fragments (30–35 nucleosomes in physiological salt (0.14 M NaCl at constant stoichiometry. Results The H1 complement of native chromatin was perturbed by adding an additional amount of one of the subtypes. A certain amount of SAR (scaffold-associated region DNA was present in the mixture to avoid precipitation of chromatin by excess H1. SAR DNA also provided a set of reference relative affinities, which were needed to estimate the relative affinities of the subtypes for chromatin from the distribution of the subtypes between the SAR and the chromatin. The amounts of chromatin, SAR and additional H1 were adjusted so as to keep the stoichiometry of perturbed chromatin similar to that of native chromatin. H1 molecules freely exchanged between the chromatin and SAR binding sites. In conditions of free exchange, H1a was the subtype of lowest affinity, H1b and H1c had intermediate affinities and H1d, H1e and H1° the highest affinities. Subtype affinities for chromatin differed by up to 19-fold. The relative affinities of the subtypes for chromatin were equivalent to those estimated for a SAR DNA fragment and a pUC19 fragment of similar length. Avian H5 had an affinity ~12-fold higher than H1e for both DNA and chromatin. Conclusion H1 subtypes freely exchange in vitro between chromatin binding sites in physiological salt (0.14 M NaCl. The large differences in relative affinity of the H1 subtypes for

  10. Enterprise architecture management

    DEFF Research Database (Denmark)

    Rahimi, Fatemeh; Gøtze, John; Møller, Charles

    2017-01-01

    Despite the growing interest in enterprise architecture management, researchers and practitioners lack a shared understanding of its applications in organizations. Building on findings from a literature review and eight case studies, we develop a taxonomy that categorizes applications of enterprise...... architecture management based on three classes of enterprise architecture scope. Organizations may adopt enterprise architecture management to help form, plan, and implement IT strategies; help plan and implement business strategies; or to further complement the business strategy-formation process....... The findings challenge the traditional IT-centric view of enterprise architecture management application and suggest enterprise architecture management as an approach that could support the consistent design and evolution of an organization as a whole....

  11. Can You Hear Architecture

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2016-01-01

    Taking an off set in the understanding of architectural quality being based on multisensory architecture, the paper aims to discuss the current acoustic discourse in inclusive design and its implications to the integration of inclusive design in architectural discourse and practice as well...... as the understanding of user needs. The paper further points to the need to elaborate and nuance the discourse much more, in order to assure inclusion to the many users living with a hearing impairment or, for other reasons, with a high degree of auditory sensitivity. Using the authors’ own research on inclusive...... design and architectural quality for people with a hearing disability and a newly conducted qualitative evaluation research in Denmark as well as architectural theories on multisensory aspects of architectural experiences, the paper uses examples of existing Nordic building cases to discuss the role...

  12. Enterprise architecture management

    DEFF Research Database (Denmark)

    Rahimi, Fatemeh; Gøtze, John; Møller, Charles

    2017-01-01

    architecture management based on three classes of enterprise architecture scope. Organizations may adopt enterprise architecture management to help form, plan, and implement IT strategies; help plan and implement business strategies; or to further complement the business strategy-formation process......Despite the growing interest in enterprise architecture management, researchers and practitioners lack a shared understanding of its applications in organizations. Building on findings from a literature review and eight case studies, we develop a taxonomy that categorizes applications of enterprise....... The findings challenge the traditional IT-centric view of enterprise architecture management application and suggest enterprise architecture management as an approach that could support the consistent design and evolution of an organization as a whole....

  13. An Architecture of Reconciliation

    OpenAIRE

    Bolton, Carlton Robert

    2001-01-01

    The reconciliation of architectural idea and built form is accomplished by the materialization of the idea through the use of specific materials with their inherent qualities and restrictions. The learning begins when one sees these restrictions not as a hinderance to the idea, but that which can reveal the very essence of Architecture. The virtue of this architecture of reconciliation lies in its ability to help Man understand his surroundings and place in the world at large. This is acc...

  14. Flexible weapons architecture design

    OpenAIRE

    Pyant, William C.

    2015-01-01

    Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilia...

  15. Architecture for the senses

    DEFF Research Database (Denmark)

    Ryhl, Camilla

    2009-01-01

    Accommodating sensory disabilities in architectural design requires specific design considerations. These are different from the ones included by the existing design concept 'accessibility', which primarily accommodates physical disabilites. Hence a new design concept 'sensory accessbility......' is presented as a parallel and complementary concept to the existing one. Sensory accessiblity accommodates sensory disabilities and describes architectural design requirements needed to ensure access to to the sensory experiences and architectural quality of a given space. The article is based on research...

  16. Architecture humanitarian emergencies

    DEFF Research Database (Denmark)

    Gomez-Guillamon, Maria; Eskemose Andersen, Jørgen; Contreras, Jorge Lobos

    2013-01-01

    Introduced by scientific articles conserning architecture and human rights in light of cultures, emergencies, social equality and sustainability, democracy, economy, artistic development and science into architecture. Concluding in definition of needs for new roles, processes and education of arc......, Architettura di Alghero in Italy, Architecture and Design of Kocaeli University in Turkey, University of Aguascalientes in Mexico, Architectura y Urbanismo of University of Chile and Escuela de Architectura of Universidad Austral in Chile....

  17. Architecture in Everyday Life

    OpenAIRE

    Costa Agarez, Ricardo

    2015-01-01

    For most architects, architecture is not only art, craft, passion and engagement; it is their ‘bread-and-butter’, too, and has been so since long. Architecture, consciously or unconsciously, is also the ‘bread-and-butter’ of communities across the world: successfully or unsuccessfully it is part of the daily lives of ordinary women and men. Yet practitioners, theoreticians and historians of architecture often disregard the more quotidian side of the discipline, a neglect that is inversely pro...

  18. The ATLAS Analysis Architecture

    International Nuclear Information System (INIS)

    Cranmer, K.S.

    2008-01-01

    We present an overview of the ATLAS analysis architecture including the relevant aspects of the computing model and the major architectural aspects of the Athena framework. Emphasis will be given to the interplay between the analysis use cases and the technical aspects of the architecture including the design of the event data model, transient-persistent separation, data reduction strategies, analysis tools, and ROOT interoperability

  19. Architecture for Data Management

    OpenAIRE

    Vukolic, Marko

    2015-01-01

    In this document we present the preliminary architecture of the SUPERCLOUD data management and storage. We start by defining the design requirements of the architecture, motivated by use cases and then review the state-of-the-art. We survey security and dependability technologies and discuss designs for the overall unifying architecture for data management that serves as an umbrella for different security and dependability data management features. Specifically the document lays out the archi...

  20. Gibberellin-induced change in the structure of chromatin in wheat sprouts: decrease in the accessibility of DNA in preparations of soluble chromatin to the action of EcoRII methylase

    International Nuclear Information System (INIS)

    Noskov, V.A.; Kintsurashvili, L.N.; Smirnova, T.A.; Manamsh'yan, T.A.; Kir'yanov, G.I.; Vanyushin, B.F.

    1986-01-01

    A method has been perfected for producing soluble chromatin from whole wheat sprouts at low ionic strength. The chromatin preparations isolated possess a native structure: they have a nucleosome organization. Under identical conditions the soluble wheat chromatin undergoes more profound degradation by DNase I and staphylococcal nuclease than the chromatin from the rat liver. The DNA contained in the isolated chromatin is capable of accepting CHnumber groups from S-[methyl- 3 H]-adenosylmethionine during incubation with DNA methylase EcoRII; not all the CC A/T GG sequences in DNA are methylated in vivo. Chromatin from gibberellin A 3 -treated wheat sprout DNA accepts 40% fewer CH 3 groups than that from the control sprouts, which is probably due to the greater compactness of the chromatin. In the case of longer incubation, the level of methylation of the chromatin falls, which may be associated with the presence of DNA-demethylating activity

  1. Architecture and Stages

    DEFF Research Database (Denmark)

    Kiib, Hans

    2009-01-01

    as "experiencescape" - a space between tourism, culture, learning and economy. Strategies related to these challenges involve new architectural concepts and art as ‘engines' for a change. New expressive architecture and old industrial buildings are often combined into hybrid narratives, linking the past...... with the future. But this is not enough. The agenda is to develop architectural spaces, where social interaction and learning are enhanced by art and fun. How can we develop new architectural designs in our inner cities and waterfronts where eventscapes, learning labs and temporal use are merged with everyday...

  2. Grid Architecture 2

    Energy Technology Data Exchange (ETDEWEB)

    Taft, Jeffrey D. [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2016-01-01

    The report describes work done on Grid Architecture under the auspices of the Department of Electricity Office of Electricity Delivery and Reliability in 2015. As described in the first Grid Architecture report, the primary purpose of this work is to provide stakeholder insight about grid issues so as to enable superior decision making on their part. Doing this requires the creation of various work products, including oft-times complex diagrams, analyses, and explanations. This report provides architectural insights into several important grid topics and also describes work done to advance the science of Grid Architecture as well.

  3. Towards a Media Architecture

    DEFF Research Database (Denmark)

    Ebsen, Tobias

    2010-01-01

    This text explores the concept of media architecture as a phenomenon of visual culture that describes the use of screen-technology in new spatial configurations in practices of architecture and art. I shall argue that this phenomenon is not necessarily a revolutionary new approach, but rather...... a result of conceptual changes in both modes visual representation and in expressions of architecture. These are changes the may be described as an evolution of ideas and consequent experiments that can be traced back to changes in the history of art and the various styles and ideologies of architecture....

  4. Decentralized Software Architecture

    National Research Council Canada - National Science Library

    Khare, Rohit

    2002-01-01

    .... While the term "decentralization" is familiar from political and economic contexts, it has been applied extensively, if indiscriminately, to describe recent trends in software architecture towards...

  5. Hi-C Chromatin Interaction Networks Predict Co-expression in the Mouse Cortex

    Science.gov (United States)

    Hulsman, Marc; Lelieveldt, Boudewijn P. F.; de Ridder, Jeroen; Reinders, Marcel

    2015-01-01

    The three dimensional conformation of the genome in the cell nucleus influences important biological processes such as gene expression regulation. Recent studies have shown a strong correlation between chromatin interactions and gene co-expression. However, predicting gene co-expression from frequent long-range chromatin interactions remains challenging. We address this by characterizing the topology of the cortical chromatin interaction network using scale-aware topological measures. We demonstrate that based on these characterizations it is possible to accurately predict spatial co-expression between genes in the mouse cortex. Consistent with previous findings, we find that the chromatin interaction profile of a gene-pair is a good predictor of their spatial co-expression. However, the accuracy of the prediction can be substantially improved when chromatin interactions are described using scale-aware topological measures of the multi-resolution chromatin interaction network. We conclude that, for co-expression prediction, it is necessary to take into account different levels of chromatin interactions ranging from direct interaction between genes (i.e. small-scale) to chromatin compartment interactions (i.e. large-scale). PMID:25965262

  6. Regular character of chromatin degradation in lymphoid tissues after treatment with biological alkylating agents in vivo

    International Nuclear Information System (INIS)

    Matyasova, J.; Skalka, M.; Cejkova, M.

    1979-01-01

    The chromatin changes are reevaluated occurring in lymphoid tissues of mice treated with alkylating agents of the nitrogen-mustard type in relation to recent evidence on the nucleosomal organization of chromatin and to our new data on the regular character of chromatin degradation in lymphoid tissues of irradiated mice. DNA was isolated from nuclei at various intervals (1 to 18 h) after treatment of mice and subjected to gel electrophoresis in polyacrylamide gels. Thymus chromatin from treated mice has been shown to degrade in a regular fashion and to yield discrete DNA fragments, resembling those that originate in lymphoid tissues of irradiated mice or in thymus nuclei digested with micrococcal nuclease in vitro. With increasing interval after treatment higher amounts of smaller DNA fragments appear. Chromatin in spleen cells responds to treatment in a similar way, whilst no degradation in vivo takes place in liver chromatin. Chromatin of LS/BL lymphosarcoma cells in mice treated with alkylating agents or with irradiation suffers from a similar regular degradation. The results stress the significance of the action of liberated or activated endogenous nuclease(s) in the development of chromatin damage in lymphoid cells after treatment with alkylating agents. (author)

  7. Functional delineation of three groups of the ATP-dependent family of chromatin remodeling enzymes.

    NARCIS (Netherlands)

    Boyer, L.A.; Logie, C.; Bonte, E; Becker, P.B.; Wade, P.A.; Wolff, A.P.; Wu, C.; Imbalzano, A.N.; Peterson, C.L.

    2000-01-01

    ATP-dependent chromatin remodeling enzymes antagonize the inhibitory effects of chromatin. We compare six different remodeling complexes: ySWI/SNF, yRSC, hSWI/SNF, xMi-2, dCHRAC, and dNURF. We find that each complex uses similar amounts of ATP to remodel nucleosomal arrays at nearly identical rates.

  8. Reading the maps: Organization and function of chromatin types in Drosophila

    NARCIS (Netherlands)

    Braunschweig, U.

    2010-01-01

    The work presented in this thesis shows that the Drosophila genome is organized in chromatin domains with many implications for gene regulation, nuclear organization, and evolution. Furthermore it provides examples of how maps of chromatin protein binding, combined with computational approaches, can

  9. Assembly of two transgenes in an artificial chromatin domain gives highly coordinated expression in tobacco

    NARCIS (Netherlands)

    Mlynárová, L.; Loonen, A.; Mietkiewska, E.; Jansen, R.C.; Nao, J.P.

    2002-01-01

    The chromatin loop model predicts that genes within the same chromatin domain exhibit coordinated regulation. We here present the first direct experimental support for this model in plants. Two reporter genes, the E. coli ß-glucuronidase gene and the firefly luciferase gene, driven by different

  10. Assembly of Two Transgenes in an Artificial Chromatin Domain Gives Highly Coordinated Expression in Tobacco

    NARCIS (Netherlands)

    Mlynárová, Ludmila; Loonen, Annelies; Mietkiewska, Elzbieta; Jansen, Ritsert C.; Nap, Jan-Peter

    The chromatin loop model predicts that genes within the same chromatin domain exhibit coordinated regulation. We here present the first direct experimental support for this model in plants. Two reporter genes, the E. coli β-glucuronidase gene and the firefly luciferase gene, driven by different

  11. Friend of Prmt1, a novel chromatin target of protein arginine methyltransferases

    NARCIS (Netherlands)

    T.B. van Dijk (Thamar); N. Gillemans (Nynke); C. Stein (Claudia); P. Fanis (Pavlos); J.A.A. Demmers (Jeroen); M.P.C. van de Corput (Mariëtte); J. Essers (Jeroen); F.G. Grosveld (Frank); U.M. Bauer (Uta-Maria); J.N.J. Philipsen (Sjaak)

    2010-01-01

    textabstractWe describe the isolation and characterization of Friend of Prmt1 (Fop), a novel chromatin target of protein arginine methyltransferases. Human Fop is encoded by C1orf77, a gene of previously unknown function. We show that Fop is tightly associated with chromatin, and that it is modified

  12. Modern human sperm freezing: Effect on DNA, chromatin and acrosome integrity

    Directory of Open Access Journals (Sweden)

    Tahereh Rahiminia

    2017-08-01

    Conclusion: Sperm in Vapour was healthier in terms of DNA, chromatin and acrosome integrity. In contrast of higher motility and normal morphology; DNA, chromatin and acrosome integrity were decreased in Vit. However, these findings were more acceptable in SSV or Vapour.

  13. High-throughput assessment of context-dependent effects of chromatin proteins

    NARCIS (Netherlands)

    Brueckner, L. (Laura); Van Arensbergen, J. (Joris); Akhtar, W. (Waseem); L. Pagie (Ludo); B. van Steensel (Bas)

    2016-01-01

    textabstractBackground: Chromatin proteins control gene activity in a concerted manner. We developed a high-throughput assay to study the effects of the local chromatin environment on the regulatory activity of a protein of interest. The assay combines a previously reported multiplexing strategy

  14. Small chromosomal regions position themselves autonomously according to their chromatin class.

    Science.gov (United States)

    van de Werken, Harmen J G; Haan, Josien C; Feodorova, Yana; Bijos, Dominika; Weuts, An; Theunis, Koen; Holwerda, Sjoerd J B; Meuleman, Wouter; Pagie, Ludo; Thanisch, Katharina; Kumar, Parveen; Leonhardt, Heinrich; Marynen, Peter; van Steensel, Bas; Voet, Thierry; de Laat, Wouter; Solovei, Irina; Joffe, Boris

    2017-06-01

    The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes. © 2017 van de Werken et al.; Published by Cold Spring Harbor Laboratory Press.

  15. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Jenna [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); Ekwall, Karl, E-mail: karl.ekwall@ki.se [Department of Biosciences and Nutrition, Center for Biosciences, Karolinska Institutet (Sweden); School of Life Sciences, University College Sodertorn, NOVUM, Huddinge (Sweden)

    2010-05-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  16. Induction of stable protein-deoxyribonucleic acid adducts in Chinese hamster cell chromatin by ultraviolet light

    International Nuclear Information System (INIS)

    Strniste, G.F.; Rall, S.C.

    1976-01-01

    Ultraviolet (uv)-light-mediated formation of protein-DNA adducts in Chinese hamster cell chromatin was investigated in an attempt to compare chromatin alterations induced in vitro with those observed in vivo. Three independent methods of analysis indicated stable protein-DNA associations: a membrane filter assay which retained DNA on the filter in the presence of high salt-detergent; a Sepharose 4B column assay in which protein eluted coincident with DNA; and a CsCl density gradient equilibrium assay which showed both protein and DNA banding at densities other than their respective native densities. Treatment of the irradiated chromatin with DNase provided further evidence that protein--DNA and not protein-protein adducts were being observed in the column assay. There is a fluence-dependent response of protein-DNA adduct formation when the chromatin is irradiated at low ionic strength and is linear for protein over the range studied. When the chromatin is exposed to differing conditions of pH, ionic strength, or divalent metal ion concentration, the quantity of adduct formed upon uv irradiation varies. Susceptibility to adduct formation can be partially explained in terms of the condensation state of the chromatin and other factors such as rearrangement, denaturation, and dissociation of the chromatin components. Besides providing information on the biological significance of these types of uv-induced lesions, this technique may be useful as a probe of chromatin structure

  17. Prediction of highly expressed genes in microbes based on chromatin accessibility

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Ussery, David

    2007-01-01

    BACKGROUND: It is well known that gene expression is dependent on chromatin structure in eukaryotes and it is likely that chromatin can play a role in bacterial gene expression as well. Here, we use a nucleosomal position preference measure of anisotropic DNA flexibility to predict highly expressed...

  18. Chromatin Controls DNA Replication Origin Selection, Lagging-Strand Synthesis, and Replication Fork Rates.

    Science.gov (United States)

    Kurat, Christoph F; Yeeles, Joseph T P; Patel, Harshil; Early, Anne; Diffley, John F X

    2017-01-05

    The integrity of eukaryotic genomes requires rapid and regulated chromatin replication. How this is accomplished is still poorly understood. Using purified yeast replication proteins and fully chromatinized templates, we have reconstituted this process in vitro. We show that chromatin enforces DNA replication origin specificity by preventing non-specific MCM helicase loading. Helicase activation occurs efficiently in the context of chromatin, but subsequent replisome progression requires the histone chaperone FACT (facilitates chromatin transcription). The FACT-associated Nhp6 protein, the nucleosome remodelers INO80 or ISW1A, and the lysine acetyltransferases Gcn5 and Esa1 each contribute separately to maximum DNA synthesis rates. Chromatin promotes the regular priming of lagging-strand DNA synthesis by facilitating DNA polymerase α function at replication forks. Finally, nucleosomes disrupted during replication are efficiently re-assembled into regular arrays on nascent DNA. Our work defines the minimum requirements for chromatin replication in vitro and shows how multiple chromatin factors might modulate replication fork rates in vivo. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  19. Chd1 remodelers maintain open chromatin and regulate the epigenetics of differentiation

    International Nuclear Information System (INIS)

    Persson, Jenna; Ekwall, Karl

    2010-01-01

    Eukaryotic DNA is packaged around octamers of histone proteins into nucleosomes, the basic unit of chromatin. In addition to enabling meters of DNA to fit within the confines of a nucleus, the structure of chromatin has functional implications for cell identity. Covalent chemical modifications to the DNA and to histones, histone variants, ATP-dependent chromatin remodelers, small noncoding RNAs and the level of chromatin compaction all contribute to chromosomal structure and to the activity or silencing of genes. These chromatin-level alterations are defined as epigenetic when they are heritable from mother to daughter cell. The great diversity of epigenomes that can arise from a single genome permits a single, totipotent cell to generate the hundreds of distinct cell types found in humans. Two recent studies in mouse and in fly have highlighted the importance of Chd1 chromatin remodelers for maintaining an open, active chromatin state. Based on evidence from fission yeast as a model system, we speculate that Chd1 remodelers are involved in the disassembly of nucleosomes at promoter regions, thus promoting active transcription and open chromatin. It is likely that these nucleosomes are specifically marked for disassembly by the histone variant H2A.Z.

  20. Initial steps of the base excision repair pathway within the nuclear architecture

    International Nuclear Information System (INIS)

    Amouroux, R.

    2009-09-01

    Oxidative stress induced lesions threaten aerobic organisms by representing a major cause of genomic instability. A common product of guanine oxidation, 8-oxo-guanine (8- oxoG) is particularly mutagenic by provoking G to T transversions. Removal of oxidised bases from DNA is initiated by the recognition and excision of the damaged base by a DNA glycosylase, initiating the base excision repair (BER) pathway. In mammals, 8-oxoG is processed by the 8-oxoG-DNA-glycosylase I (OGG1), which biochemical mechanisms has been well characterised in vitro. However how and where this enzyme finds the modified base within the complex chromatin architecture is not yet understood. We show that upon induction of 8-oxoG, OGG1, together with at least two other proteins involved in BER, is recruited from a soluble fraction to chromatin. Formation kinetics of this patches correlates with 8-oxoG excision, suggesting a direct link between presence of this chromatin-associated complexes and 8-oxoG repair. More precisely, these repair patches are specifically directed to euchromatin regions, and completely excluded from heterochromatin regions. Inducing of artificial chromatin compaction results in a complete inhibition of the in vivo repair of 8-oxoG, probably by impeding the access of OGG1 to the lesion. Using OGG1 mutants, we show that OGG1 direct recognition of 8-oxoG did not trigger its re-localisation to the chromatin. We conclude that in response to the induction of oxidative DNA damage, the DNA glycosylase is actively recruited to regions of open chromatin allowing the access of the BER machinery to the lesions. (author)

  1. Toxic effects of lead and nickel nitrate on rat liver chromatin components.

    Science.gov (United States)

    Rabbani-Chadegani Iii, Azra; Fani, Nesa; Abdossamadi, Sayeh; Shahmir, Nosrat

    2011-01-01

    The biological activity of heavy metals is related to their physicochemical interaction with biological receptors. In the present study, the effect of low concentrations of nickel nitrate and lead nitrate (lead nitrate to chromatin compared to nickel nitrate. Also, the binding affinity of lead nitrate to histone proteins free in solution was higher than nickel. On the basis of the results, it is concluded that lead reacts with chromatin components even at very low concentrations and induce chromatin aggregation through histone-DNA cross-links. Whereas, nickel nitrate is less effective on chromatin at low concentrations, suggesting higher toxicity of lead nitrate on chromatin compared to nickel. Copyright © 2010 Wiley Periodicals, Inc.

  2. High-Frequency Promoter Firing Links THO Complex Function to Heavy Chromatin Formation

    DEFF Research Database (Denmark)

    Mouaikel, John; Causse, Sébastien Z; Rougemaille, Mathieu

    2013-01-01

    The THO complex is involved in transcription, genome stability, and messenger ribonucleoprotein (mRNP) formation, but its precise molecular function remains enigmatic. Under heat shock conditions, THO mutants accumulate large protein-DNA complexes that alter the chromatin density of target genes...... (heavy chromatin), defining a specific biochemical facet of THO function and a powerful tool of analysis. Here, we show that heavy chromatin distribution is dictated by gene boundaries and that the gene promoter is necessary and sufficient to convey THO sensitivity in these conditions. Single......-molecule fluorescence insitu hybridization measurements show that heavy chromatin formation correlates with an unusually high firing pace of the promoter with more than 20 transcription events per minute. Heavy chromatin formation closely follows the modulation of promoter firing and strongly correlates with polymerase...

  3. Time-resolved spectroscopy and fluorescence resonance energy transfer in the study of excimer laser damage of chromatin

    Energy Technology Data Exchange (ETDEWEB)

    Radu, L. [Department of Molecular Genetics and Radiobiology, Babes National Institute, Bucharest (Romania)], E-mail: lilianajradu@yahoo.fr; Mihailescu, I. [Department of Lasers, Laser, Plasma and Radiation Physics Institute, Bucharest (Romania); Radu, S. [Department of Computer Science, Polytechnics University, Bucharest (Romania); Gazdaru, D. [Department of Biophysics, Bucharest University (Romania)

    2007-09-21

    The analysis of chromatin damage produced by a 248 nm excimer laser radiation, for doses of 0.3-3 MJ/m{sup 2} was carried out by time-resolved spectroscopy and fluorescence resonance energy transfer (FRET). The chromatin was extracted from a normal and a tumoral tissue of Wistar rats. The decrease with laser dose of the relative contribution of the excited state lifetimes of ethidium bromide (EtBr) bounded to chromatin constitutes an evidence of the reduction of chromatin deoxyribonucleic acid (DNA) double-strand structure. FRET was performed from dansyl chloride to acridine orange, both coupled to chromatin. The increase of the average distance between these ligands, under the action of laser radiation, reflects a loosening of the chromatin structure. The radiosensitivity of tumor tissue chromatin is higher than that of a normal tissue. The determination of the chromatin structure modification in an excimer laser field can be of interest in laser therapy.

  4. Time-resolved spectroscopy and fluorescence resonance energy transfer in the study of excimer laser damage of chromatin

    International Nuclear Information System (INIS)

    Radu, L.; Mihailescu, I.; Radu, S.; Gazdaru, D.

    2007-01-01

    The analysis of chromatin damage produced by a 248 nm excimer laser radiation, for doses of 0.3-3 MJ/m 2 was carried out by time-resolved spectroscopy and fluorescence resonance energy transfer (FRET). The chromatin was extracted from a normal and a tumoral tissue of Wistar rats. The decrease with laser dose of the relative contribution of the excited state lifetimes of ethidium bromide (EtBr) bounded to chromatin constitutes an evidence of the reduction of chromatin deoxyribonucleic acid (DNA) double-strand structure. FRET was performed from dansyl chloride to acridine orange, both coupled to chromatin. The increase of the average distance between these ligands, under the action of laser radiation, reflects a loosening of the chromatin structure. The radiosensitivity of tumor tissue chromatin is higher than that of a normal tissue. The determination of the chromatin structure modification in an excimer laser field can be of interest in laser therapy

  5. Snake-like chromatin in conjunctival cells of a population aged 30-60 years from Copenhagen City

    DEFF Research Database (Denmark)

    Bjerrum, Kirsten Birgitte

    1998-01-01

    ophthalmology, keratoconjunctivitis sicca, Sjögrens Syndrome, epidemiology, imprint biopsy, snake-like chromatin......ophthalmology, keratoconjunctivitis sicca, Sjögrens Syndrome, epidemiology, imprint biopsy, snake-like chromatin...

  6. Elucidation of Chromatin Remodeling Machinery Involved in Regulation of Estrogen Receptor Alpha Expression in Human Breast Cancer Cells

    National Research Council Canada - National Science Library

    Sharma, Dipali

    2005-01-01

    .... Using chromatin immunoprecipitation (ChIP), we examined the chromatin status and repressor complex associated with silenced ER and changes in the key regulatory factors during reactivation by inhibitors of DNMT...

  7. Cytology of DNA Replication Reveals Dynamic Plasticity of Large-Scale Chromatin Fibers.

    Science.gov (United States)

    Deng, Xiang; Zhironkina, Oxana A; Cherepanynets, Varvara D; Strelkova, Olga S; Kireev, Igor I; Belmont, Andrew S

    2016-09-26

    In higher eukaryotic interphase nuclei, the 100- to >1,000-fold linear compaction of chromatin is difficult to reconcile with its function as a template for transcription, replication, and repair. It is challenging to imagine how DNA and RNA polymerases with their associated molecular machinery would move along the DNA template without transient decondensation of observed large-scale chromatin "chromonema" fibers [1]. Transcription or "replication factory" models [2], in which polymerases remain fixed while DNA is reeled through, are similarly difficult to conceptualize without transient decondensation of these chromonema fibers. Here, we show how a dynamic plasticity of chromatin folding within large-scale chromatin fibers allows DNA replication to take place without significant changes in the global large-scale chromatin compaction or shape of these large-scale chromatin fibers. Time-lapse imaging of lac-operator-tagged chromosome regions shows no major change in the overall compaction of these chromosome regions during their DNA replication. Improved pulse-chase labeling of endogenous interphase chromosomes yields a model in which the global compaction and shape of large-Mbp chromatin domains remains largely invariant during DNA replication, with DNA within these domains undergoing significant movements and redistribution as they move into and then out of adjacent replication foci. In contrast to hierarchical folding models, this dynamic plasticity of large-scale chromatin organization explains how localized changes in DNA topology allow DNA replication to take place without an accompanying global unfolding of large-scale chromatin fibers while suggesting a possible mechanism for maintaining epigenetic programming of large-scale chromatin domains throughout DNA replication. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Transcriptional and chromatin regulation during fasting – The genomic era

    Science.gov (United States)

    Goldstein, Ido; Hager, Gordon L.

    2015-01-01

    An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant upon transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis and amino acid shuttling. We summarize the recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the summarized findings reveal a large degree of co-operation between TFs during fasting which occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response. PMID:26520657

  9. Increased polyamines alter chromatin and stabilize autoantigens in autoimmune diseases

    Directory of Open Access Journals (Sweden)

    Wesley H. Brooks

    2013-04-01

    Full Text Available Polyamines are small cations with unique combinations of charge and length that give them many putative interactions in cells. Polyamines are essential since they are involved in replication, transcription, translation, and stabilization of macro-molecular complexes. However, polyamine synthesis competes with cellular methylation for S-adenosylmethionine, the methyl donor. Also, polyamine degradation can generate reactive molecules like acrolein. Therefore, polyamine levels are tightly controlled. This control may be compromised in autoimmune diseases since elevated polyamine levels are seen in autoimmune diseases. Here a hypothesis is presented explaining how polyamines can stabilize autoantigens. In addition, the hypothesis explains how polyamines can inappropriately activate enzymes involved in NETosis, a process in which chromatin is modified and extruded from cells as extracellular traps that bind pathogens during an immune response. This polyamine-induced enzymatic activity can lead to an increase in NETosis resulting in release of autoantigenic material and tissue damage.

  10. Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

    Directory of Open Access Journals (Sweden)

    Li Shen

    2013-06-01

    Full Text Available A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE, recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

  11. Causes and consequences of chromatin variation between inbred mice.

    Directory of Open Access Journals (Sweden)

    Mona Hosseini

    2013-06-01

    Full Text Available Variation at regulatory elements, identified through hypersensitivity to digestion by DNase I, is believed to contribute to variation in complex traits, but the extent and consequences of this variation are poorly characterized. Analysis of terminally differentiated erythroblasts in eight inbred strains of mice identified reproducible variation at approximately 6% of DNase I hypersensitive sites (DHS. Only 30% of such variable DHS contain a sequence variant predictive of site variation. Nevertheless, sequence variants within variable DHS are more likely to be associated with complex traits than those in non-variant DHS, and variants associated with complex traits preferentially occur in variable DHS. Changes at a small proportion (less than 10% of variable DHS are associated with changes in nearby transcriptional activity. Our results show that whilst DNA sequence variation is not the major determinant of variation in open chromatin, where such variants exist they are likely to be causal for complex traits.

  12. Chromatin Dynamics in Vivo: A Game of Musical Chairs

    Directory of Open Access Journals (Sweden)

    Daniël P. Melters

    2015-08-01

    Full Text Available Histones are a major component of chromatin, the nucleoprotein complex fundamental to regulating transcription, facilitating cell division, and maintaining genome integrity in almost all eukaryotes. In addition to canonical, replication-dependent histones, replication-independent histone variants exist in most eukaryotes. In recent years, steady progress has been made in understanding how histone variants assemble, their involvement in development, mitosis, transcription, and genome repair. In this review, we will focus on the localization of the major histone variants H3.3, CENP-A, H2A.Z, and macroH2A, as well as how these variants have evolved, their structural differences, and their functional significance in vivo.

  13. [Effect of irradiation on the degradation of rat thymocyte chromatin].

    Science.gov (United States)

    Tsudzevich, B O; Parkhomets', Iu P; Andriĭchuk, T R; Iurkina, V V

    1998-01-01

    Genome instability of adaptive nature is formed under the experimental influence on a cell. Under critical conditions, strategy of organism is to damage the cells that cannot be restored and controlled by including the program of apoptosis. The ordered internucleosomal DNA degradation is considered to be one of the proof attributes of immunocompetent cell apoptosis. We investigated the effects of various doses of irradiation on the thymocytes chromatine fragmentation in 1,2,3 hours after a single X-ray exposure or after chronic influence in conditions of Chernobyl research base. By the means of electrophoresis in agarose and judging by polydeoxyribonucleotides accumulation we observed the "ladder pattern" of degradation in 3 hr after single 1 Gr irradiation (the smallest dose displaying the effect). We suppose that the influence of both chronic low-intensity irradiation taking place in Chernobyl and single X-ray exposure result in intensifying of DNA fragmentation in the cells of immunocompetent organs.

  14. Chromatin Constrains the Initiation and Elongation of DNA Replication.

    Science.gov (United States)

    Devbhandari, Sujan; Jiang, Jieqing; Kumar, Charanya; Whitehouse, Iestyn; Remus, Dirk

    2017-01-05

    Eukaryotic chromosomal DNA is faithfully replicated in a complex series of cell-cycle-regulated events that are incompletely understood. Here we report the reconstitution of DNA replication free in solution with purified proteins from the budding yeast Saccharomyces cerevisiae. The system recapitulates regulated bidirectional origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases Pol α, Pol δ, and Pol ε; and canonical maturation of Okazaki fragments into continuous daughter strands. We uncover a dual regulatory role for chromatin during DNA replication: promoting origin dependence and determining Okazaki fragment length by restricting Pol δ progression. This system thus provides a functional platform for the detailed mechanistic analysis of eukaryotic chromosome replication. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Chromatin in fractal globule state: evidence from comet assay

    Directory of Open Access Journals (Sweden)

    Afanasieva K. S.

    2015-04-01

    Full Text Available At higher order levels chromatin is organized into loops that appear as a result of contacts between distant loci. The aim of this work was to investigate the length distribution of the DNA loops in nucleoids obtained after lysis of either whole cells or isolated cell nuclei. Methods. We used single cell gel electrophoresis to analyze the kinetics of the DNA loop migration from the two nucleoid types. Results. The kinetics of the DNA exit was found to have specific features for the two types of nucleoids. At the same time, in both cases, the DNA amount in the electrophoretic track depends linearly on the length of the longest loops in the track. Conclusions. We have concluded that for the loops up to ~ 100 kb the length distribution appears to be consistent with the fractal globule organization.

  16. Pyrimidine dimers in Drosophila chromatin become increasingly accessible after irradiation

    International Nuclear Information System (INIS)

    Harris, P.V.; Boyd, J.B.

    1987-01-01

    A prokaryotic DNA-repair enzyme has been utilized as a probe for changes in the accessibility of pyrimidine dimers in Drosophila chromatin following UV irradiation. The results demonstrate a rapid cellular response to physiologically relevant doses of radiation which results in at least a 40% increase in accessible dimers. This increase occurs in two incision-deficient mutants which indicates that the excision-repair process, at or beyond the incision step, is not required or responsible for the increase. In the absence of excision the increase in accessibility persists for a least 2 days following irradiation. The observed increase in accessibility is inhibited by both novobiocin and coumermycin. These inhibitors do not inhibit the initial rate of incision, but do reduce dimer excision measured over more extended periods. A pre-incision process is proposed which actively exposes DNA lesions to excision repair. A fraction of the genome is postulated to be accessible without the intervention of that process. (Auth.)

  17. Comparative transmission genetics of introgressed chromatin in Gossypium (cotton) polyploids.

    Science.gov (United States)

    Waghmare, Vijay N; Rong, Junkang; Rogers, Carl J; Bowers, John E; Chee, Peng W; Gannaway, John R; Katageri, Ishwarappa; Paterson, Andrew H

    2016-04-01

    Introgression is widely acknowledged as a potential source of valuable genetic variation, and growing effort is being invested in analysis of interspecific crosses conferring transgressive variation. Experimental backcross populations provide an opportunity to study transmission genetics following interspecific hybridization, identifying opportunities and constraints to introgressive crop improvement. The evolutionary consequences of introgression have been addressed at the theoretical level, however, issues related to levels and patterns of introgression among (plant) species remain inadequately explored, including such factors as polyploidization, subgenome interaction inhabiting a common nucleus, and the genomic distribution and linkage relationships of introgressant alleles. We analyze introgression into the polyploid Gossypium hirsutum (upland cotton) from its sister G. tomentosum and compare the level and pattern with that of G. barbadense representing a different clade tracing to the same polyploidization. Across the genome, recurrent backcrossing to Gossypium hirsutum yielded only one-third of the expected average frequency of the G. tomentosum allele, although one unusual region showed preferential introgression. Although a similar rate of introgression is found in the two subgenomes of polyploid (AtDt) G. hirsutum, a preponderance of multilocus interactions were largely within the Dt subgenome. Skewed G. tomentosum chromatin transmission is polymorphic among two elite G. hirsutum genotypes, which suggests that genetic background may profoundly affect introgression of particular chromosomal regions. Only limited correspondence is found between G. hirsutum chromosomal regions that are intolerant to introgression from the two species, G. barbadense and G. tomentosum, concentrated near possible inversion polymorphisms. Complex transmission of introgressed chromatin highlights the challenges to utilization of exotic germplasm in crop improvement. © 2016

  18. Chromatin immunoprecipitation to analyze DNA binding sites of HMGA2.

    Directory of Open Access Journals (Sweden)

    Nina Winter

    Full Text Available BACKGROUND: HMGA2 is an architectonic transcription factor abundantly expressed during embryonic and fetal development and it is associated with the progression of malignant tumors. The protein harbours three basically charged DNA binding domains and an acidic protein binding C-terminal domain. DNA binding induces changes of DNA conformation and hence results in global overall change of gene expression patterns. Recently, using a PCR-based SELEX (Systematic Evolution of Ligands by Exponential Enrichment procedure two consensus sequences for HMGA2 binding have been identified. METHODOLOGY/PRINCIPAL FINDINGS: In this investigation chromatin immunoprecipitation (ChIP experiments and bioinformatic methods were used to analyze if these binding sequences can be verified on chromatin of living cells as well. CONCLUSION: After quantification of HMGA2 protein in different cell lines the colon cancer derived cell line HCT116 was chosen for further ChIP experiments because of its 3.4-fold higher HMGA2 protein level. 49 DNA fragments were obtained by ChIP. These fragments containing HMGA2 binding sites have been analyzed for their AT-content, location in the human genome and similarities to sequences generated by a SELEX study. The sequences show a significantly higher AT-content than the average of the human genome. The artificially generated SELEX sequences and short BLAST alignments (11 and 12 bp of the ChIP fragments from living cells show similarities in their organization. The flanking regions are AT-rich, whereas a lower conservation is present in the center of the sequences.

  19. Alternative epigenetic chromatin states of polycomb target genes.

    Directory of Open Access Journals (Sweden)

    Yuri B Schwartz

    2010-01-01

    Full Text Available Polycomb (PcG regulation has been thought to produce stable long-term gene silencing. Genomic analyses in Drosophila and mammals, however, have shown that it targets many genes, which can switch state during development. Genetic evidence indicates that critical for the active state of PcG target genes are the histone methyltransferases Trithorax (TRX and ASH1. Here we analyze the repertoire of alternative states in which PcG target genes are found in different Drosophila cell lines and the role of PcG proteins TRX and ASH1 in controlling these states. Using extensive genome-wide chromatin immunoprecipitation analysis, RNAi knockdowns, and quantitative RT-PCR, we show that, in addition to the known repressed state, PcG targets can reside in a transcriptionally active state characterized by formation of an extended domain enriched in ASH1, the N-terminal, but not C-terminal moiety of TRX and H3K27ac. ASH1/TRX N-ter domains and transcription are not incompatible with repressive marks, sometimes resulting in a "balanced" state modulated by both repressors and activators. Often however, loss of PcG repression results instead in a "void" state, lacking transcription, H3K27ac, or binding of TRX or ASH1. We conclude that PcG repression is dynamic, not static, and that the propensity of a target gene to switch states depends on relative levels of PcG, TRX, and activators. N-ter TRX plays a remarkable role that antagonizes PcG repression and preempts H3K27 methylation by acetylation. This role is distinct from that usually attributed to TRX/MLL proteins at the promoter. These results have important implications for Polycomb gene regulation, the "bivalent" chromatin state of embryonic stem cells, and gene expression in development.

  20. Distributed probing of chromatin structure in vivo reveals pervasive chromatin accessibility for expressed and non-expressed genes during tissue differentiation in C. elegans

    Directory of Open Access Journals (Sweden)

    Sha Ky

    2010-08-01

    Full Text Available Abstract Background Tissue differentiation is accompanied by genome-wide changes in the underlying chromatin structure and dynamics, or epigenome. By controlling when, where, and what regulatory factors have access to the underlying genomic DNA, the epigenome influences the cell's transcriptome and ultimately its function. Existing genomic methods for analyzing cell-type-specific changes in chromatin generally involve two elements: (i a source for purified cells (or nuclei of distinct types, and (ii a specific treatment that partitions or degrades chromatin by activity or structural features. For many cell types of great interest, such assays are limited by our inability to isolate the relevant cell populations in an organism or complex tissue containing an intertwined mixture of other cells. This limitation has confined available knowledge of chromatin dynamics to a narrow range of biological systems (cell types that can be sorted/separated/dissected in large numbers and tissue culture models or to amalgamations of diverse cell types (tissue chunks, whole organisms. Results Transgene-driven expression of DNA/chromatin modifying enzymes provides one opportunity to query chromatin structures in expression-defined cell subsets. In this work we combine in vivo expression of a bacterial DNA adenine methyltransferase (DAM with high throughput sequencing to sample tissue-specific chromatin accessibility on a genome-wide scale. We have applied the method (DALEC: Direct Asymmetric Ligation End Capture towards mapping a cell-type-specific view of genome accessibility as a function of differentiated state. Taking advantage of C. elegans strains expressing the DAM enzyme in diverse tissues (body wall muscle, gut, and hypodermis, our efforts yield a genome-wide dataset measuring chromatin accessibility at each of 538,000 DAM target sites in the C. elegans (diploid genome. Conclusions Validating the DALEC mapping results, we observe a strong association

  1. Architecture and Intelligentsia

    Directory of Open Access Journals (Sweden)

    Alexander Rappaport

    2015-08-01

    Full Text Available The article observes intellectual and cultural level of architecture and its important functions in social process. Historical analysis shows constant decline of intellectual level of profession, as a reaction on radical changes in its social functions and mass scale, leading to degrading of individual critical reflection and growing dependence of architecture to political and economical bureaucracy.

  2. Architecture and Intelligentsia

    OpenAIRE

    Alexander Rappaport

    2015-01-01

    The article observes intellectual and cultural level of architecture and its important functions in social process. Historical analysis shows constant decline of intellectual level of profession, as a reaction on radical changes in its social functions and mass scale, leading to degrading of individual critical reflection and growing dependence of architecture to political and economical bureaucracy.

  3. OS Friendly Microprocessor Architecture

    Science.gov (United States)

    2017-04-01

    NOTES Patrick La Fratta is now affiliated with Micron Technology, Inc., Boise, Idaho. 14. ABSTRACT We present an introduction to the patented ...Operating System Friendly Microprocessor Architecture (OSFA). The software framework to support the hardware-level security features is currently patent ...Army is assignee. OS Friendly Microprocessor Architecture. United States Patent 9122610. 2015 Sep. 2. Jungwirth P, inventor; US Army is assignee

  4. Architecture, Drawing, Topology

    DEFF Research Database (Denmark)

    Meldgaard, Morten

    This book presents contributions of drawing and text along with their many relationalities from ontology to history and vice versa in a range of reflections on architecture, drawing and topology. We hope to thereby indicate the potential of the theme in understanding not only the architecture of ...

  5. Software Architecture Evolution

    Science.gov (United States)

    Barnes, Jeffrey M.

    2013-01-01

    Many software systems eventually undergo changes to their basic architectural structure. Such changes may be prompted by new feature requests, new quality attribute requirements, changing technology, or other reasons. Whatever the causes, architecture evolution is commonplace in real-world software projects. Today's software architects, however,…

  6. FTS2000 network architecture

    Science.gov (United States)

    Klenart, John

    1991-01-01

    The network architecture of FTS2000 is graphically depicted. A map of network A topology is provided, with interservice nodes. Next, the four basic element of the architecture is laid out. Then, the FTS2000 time line is reproduced. A list of equipment supporting FTS2000 dedicated transmissions is given. Finally, access alternatives are shown.

  7. Adaptive Architectural Envelope

    DEFF Research Database (Denmark)

    Foged, Isak Worre; Kirkegaard, Poul Henning

    2010-01-01

    . The general scopes of this paper are to develop a new adaptive kinetic architectural structure, particularly a reconfigurable architectural structure which can transform body shape from planar geometries to hyper-surfaces using different control strategies, i.e. a transformation into more than one or two...

  8. Architecture and energy

    DEFF Research Database (Denmark)

    Marsh, Rob; Lauring, Michael

    2011-01-01

    Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies.......Traditional low-energy architecture has not necessarily led to reduced energy consumption. A paradigm shift is proposed promoting pluralistic energy-saving strategies....

  9. Re[valuating]-architecture

    NARCIS (Netherlands)

    Pereira Roders, A.R.; Post, J.M.; Erkelens, P.A.; Haugen, T.I.

    2006-01-01

    The architectural hierarchy of aims altered in the last decades. Quality and comfort have dethroned functionality! We are already familiar with the taxonomy – quality certification in the construction world; but in architectural designs, it is not common to evaluate scientifically, if the design has

  10. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2014-07-01

    Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisation focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means.In this context, this sixth Footprint issue examines the influence of digital means as pragmatic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

  11. Digitally-Driven Architecture

    Directory of Open Access Journals (Sweden)

    Henriette Bier

    2010-06-01

    Full Text Available The shift from mechanical to digital forces architects to reposition themselves: Architects generate digital information, which can be used not only in designing and fabricating building components but also in embedding behaviours into buildings. This implies that, similar to the way that industrial design and fabrication with its concepts of standardisation and serial production influenced modernist architecture, digital design and fabrication influences contemporary architecture. While standardisa­tion focused on processes of rationalisation of form, mass-customisation as a new paradigm that replaces mass-production, addresses non-standard, complex, and flexible designs. Furthermore, knowledge about the designed object can be encoded in digital data pertaining not just to the geometry of a design but also to its physical or other behaviours within an environment. Digitally-driven architecture implies, therefore, not only digitally-designed and fabricated architecture, it also implies architecture – built form – that can be controlled, actuated, and animated by digital means. In this context, this sixth Footprint issue examines the influence of digital means as prag­matic and conceptual instruments for actuating architecture. The focus is not so much on computer-based systems for the development of architectural designs, but on architecture incorporating digital control, sens­ing, actuating, or other mechanisms that enable buildings to inter­act with their users and surroundings in real time in the real world through physical or sensory change and variation.

  12. Architecture in Everyday Life

    NARCIS (Netherlands)

    Agarez, R.; Mota, N.

    2015-01-01

    For most architects, architecture is not only art, craft, passion and engagement; it is their ‘bread-and-butter’, too, and has been so since long. Architecture, consciously or unconsciously, is also the ‘bread-and-butter’ of communities across the world: successfully or unsuccessfully it is part of

  13. Enterprise architecture intelligence

    NARCIS (Netherlands)

    Veneberg, R.K.M.; Iacob, Maria Eugenia; van Sinderen, Marten J.; Bodenstaff, L.; Reichert, M.U.; Rinderle-Ma, S.; Grossmann, G.

    2014-01-01

    Combining enterprise architecture and operational data is complex (especially when considering the actual ‘matching’ of data with enterprise architecture objects), and little has been written on how to do this. Therefore, in this paper we aim to fill this gap and propose a method to combine

  14. Information Architecture: Looking Ahead.

    Science.gov (United States)

    Rosenfeld, Louis

    2002-01-01

    Considers the future of the field of information architecture. Highlights include a comparison with the growth of the field of professional management; the design of information systems since the Web; more demanding users; the need for an interdisciplinary approach; and how to define information architecture. (LRW)

  15. Architectural Physics: Lighting.

    Science.gov (United States)

    Hopkinson, R. G.

    The author coordinates the many diverse branches of knowledge which have dealt with the field of lighting--physiology, psychology, engineering, physics, and architectural design. Part I, "The Elements of Architectural Physics", discusses the physiological aspects of lighting, visual performance, lighting design, calculations and measurements of…

  16. Architecture or Sculpture?

    DEFF Research Database (Denmark)

    Baumeister, Ruth

    2014-01-01

    Jørn Utzon´s museum design for Asger Jorn´s collection in Silkeborg contextualized in the postwar context of an organic architecture.......Jørn Utzon´s museum design for Asger Jorn´s collection in Silkeborg contextualized in the postwar context of an organic architecture....

  17. Globalization and Landscape Architecture

    OpenAIRE

    Robert R. Hewitt

    2014-01-01

    The literature review examines globalization and landscape architecture as discourse, samples its various meanings, and proposes methods to identify and contextualize its specific literature. Methodologically, the review surveys published articles and books by leading authors and within the WorldCat.org Database associated with landscape architecture and globalization, analyzing survey results for comprehensive concept...

  18. Research Through Architecture

    DEFF Research Database (Denmark)

    Peder Pedersen, Claus

    2018-01-01

    Presentation of the PhD research at the Aarhus School of Architecture and selected PhD projects in relation to PhD exhibition at Godsbanen.......Presentation of the PhD research at the Aarhus School of Architecture and selected PhD projects in relation to PhD exhibition at Godsbanen....

  19. Aesthetics of sustainable architecture

    NARCIS (Netherlands)

    Lee, S.; Hill, G.; Sauerbruch, M.; Hutton, L.; Knowles, R.; Bothwell, K.; Brennan, J.; Jauslin, D.; Holzheu, H.; AlSayyad, N.; Arboleda, G.; Bharne, V.; Røstvik, H.; Kuma, K.; Sunikka-Blank, M.; Glaser, M.; Pero, E.; Sjkonsberg, M.; Teuffel, P.; Mangone, G.; Finocchiaro, L.; Hestnes, A.; Briggs, D.; Frampton, K.; Lee, S.

    2011-01-01

    The purpose of this book is to reveal, explore and further the debate on the aesthetic potentials of sustainable architecture and its practice. This book opens a new area of scholarship and discourse in the design and production of sustainable architecture, one that is based in aesthetics. The

  20. Teaching American Indian Architecture.

    Science.gov (United States)

    Winchell, Dick

    1991-01-01

    Reviews "Native American Architecture," by Nabokov and Easton, an encyclopedic work that examines technology, climate, social structure, economics, religion, and history in relation to house design and the "meaning" of space among tribes of nine regions. Describes this book's use in a college course on Native American architecture. (SV)

  1. Snake-like chromatin in conjunctival cells of normal elderly persons and of patients with primary Sjögren's syndrome and other connective tissue diseases

    DEFF Research Database (Denmark)

    Bjerrum, Kirsten Birgitte

    1995-01-01

    Ophthalmology, snake-like chromatin, cytoplasm ratio, keratoconjunctivitis sicca, nucleus, goblet cell......Ophthalmology, snake-like chromatin, cytoplasm ratio, keratoconjunctivitis sicca, nucleus, goblet cell...

  2. Diversity among POU transcription factors in chromatin recognition and cell fate reprogramming.

    Science.gov (United States)

    Malik, Vikas; Zimmer, Dennis; Jauch, Ralf

    2018-05-01

    The POU (Pit-Oct-Unc) protein family is an evolutionary ancient group of transcription factors (TFs) that bind specific DNA sequences to direct gene expression programs. The fundamental importance of POU TFs to orchestrate embryonic development and to direct cellular fate decisions is well established, but the molecular basis for this activity is insufficiently understood. POU TFs possess a bipartite 'two-in-one' DNA binding domain consisting of two independently folding structural units connected by a poorly conserved and flexible linker. Therefore, they represent a paradigmatic example to study the molecular basis for the functional versatility of TFs. Their modular architecture endows POU TFs with the capacity to accommodate alternative composite DNA sequences by adopting different quaternary structures. Moreover, associations with partner proteins crucially influence the selection of their DNA binding sites. The plentitude of DNA binding modes confers the ability to POU TFs to regulate distinct genes in the context of different cellular environments. Likewise, different binding modes of POU proteins to DNA could trigger alternative regulatory responses in the context of different genomic locations of the same cell. Prominent POU TFs such as Oct4, Brn2, Oct6 and Brn4 are not only essential regulators of development but have also been successfully employed to reprogram somatic cells to pluripotency and neural lineages. Here we review biochemical, structural, genomic and cellular reprogramming studies to examine how the ability of POU TFs to select regulatory DNA, alone or with partner factors, is tied to their capacity to epigenetically remodel chromatin and drive specific regulatory programs that give cells their identities.

  3. Knowledge and Architectural Practice

    DEFF Research Database (Denmark)

    Verbeke, Johan

    2017-01-01

    of the level of research methods and will explain that the research methods and processes in creative practice research are very similar to grounded theory which is an established research method in the social sciences. Finally, an argument will be made for a more explicit research attitude in architectural......This paper focuses on the specific knowledge residing in architectural practice. It is based on the research of 35 PhD fellows in the ADAPT-r (Architecture, Design and Art Practice Training-research) project. The ADAPT-r project innovates architectural research in combining expertise from academia...... and from practice in order to highlight and extract the specific kind of knowledge which resides and is developed in architectural practice (creative practice research). The paper will discuss three ongoing and completed PhD projects and focusses on the outcomes and their contribution to the field...

  4. Product Architecture Modularity Strategies

    DEFF Research Database (Denmark)

    Mikkola, Juliana Hsuan

    2003-01-01

    The focus of this paper is to integrate various perspectives on product architecture modularity into a general framework, and also to propose a way to measure the degree of modularization embedded in product architectures. Various trade-offs between modular and integral product architectures...... and how components and interfaces influence the degree of modularization are considered. In order to gain a better understanding of product architecture modularity as a strategy, a theoretical framework and propositions are drawn from various academic literature sources. Based on the literature review......, the following key elements of product architecture are identified: components (standard and new-to-the-firm), interfaces (standardization and specification), degree of coupling, and substitutability. A mathematical function, termed modularization function, is introduced to measure the degree of modularization...

  5. Can architecture be barbaric?

    Science.gov (United States)

    Hürol, Yonca

    2009-06-01

    The title of this article is adapted from Theodor W. Adorno's famous dictum: 'To write poetry after Auschwitz is barbaric.' After the catastrophic earthquake in Kocaeli, Turkey on the 17th of August 1999, in which more than 40,000 people died or were lost, Necdet Teymur, who was then the dean of the Faculty of Architecture of the Middle East Technical University, referred to Adorno in one of his 'earthquake poems' and asked: 'Is architecture possible after 17th of August?' The main objective of this article is to interpret Teymur's question in respect of its connection to Adorno's philosophy with a view to make a contribution to the politics and ethics of architecture in Turkey. Teymur's question helps in providing a new interpretation of a critical approach to architecture and architectural technology through Adorno's philosophy. The paper also presents a discussion of Adorno's dictum, which serves for a better understanding of its universality/particularity.

  6. Architecture in the Islamic Civilization: Muslim Building or Islamic Architecture

    OpenAIRE

    Yassin, Ayat Ali; Utaberta, Dr. Nangkula

    2012-01-01

    The main problem of the theory in the arena of islamic architecture is affected by some of its Westernthoughts, and stereotyping the islamic architecture according to Western thoughts; this leads to the breakdownof the foundations in the islamic architecture. It is a myth that islamic architecture is subjected to theinfluence from foreign architectures. This paper will highlight the dialectical concept of islamic architecture ormuslim buildings and the areas of recognition in islamic architec...

  7. Minimalism in architecture: Abstract conceptualization of architecture

    Directory of Open Access Journals (Sweden)

    Vasilski Dragana

    2015-01-01

    Full Text Available Minimalism in architecture contains the idea of the minimum as a leading creative tend to be considered and interpreted in working through phenomena of empathy and abstraction. In the Western culture, the root of this idea is found in empathy of Wilhelm Worringer and abstraction of Kasimir Malevich. In his dissertation, 'Abstraction and Empathy' Worringer presented his thesis on the psychology of style through which he explained the two opposing basic forms: abstraction and empathy. His conclusion on empathy as a psychological basis of observation expression is significant due to the verbal congruence with contemporary minimalist expression. His intuition was enhenced furthermore by figure of Malevich. Abstraction, as an expression of inner unfettered inspiration, has played a crucial role in the development of modern art and architecture of the twentieth century. Abstraction, which is one of the basic methods of learning in psychology (separating relevant from irrelevant features, Carl Jung is used to discover ideas. Minimalism in architecture emphasizes the level of abstraction to which the individual functions are reduced. Different types of abstraction are present: in the form as well as function of the basic elements: walls and windows. The case study is an example of Sou Fujimoto who is unequivocal in its commitment to the autonomy of abstract conceptualization of architecture.

  8. Karyometry detects subvisual differences in chromatin organization state between cribriform and flat high-grade prostatic intraepithelial neoplasia.

    Science.gov (United States)

    Montironi, Rodolfo; Thompson, Deborah; Scarpelli, Marina; Mazzucchelli, Roberta; Peketi, Prasanthi; Hamilton, Peter W; Bostwick, David G; Bartels, Peter H

    2004-08-01

    This digital texture analysis-based study evaluates the chromatin organization state in flat and cribriform high-grade prostatic intraepithelial neoplasia (PIN), in the adjacent normal looking secretory epithelium and in the co-occurring adenocarcinoma. Digital texture analysis (karyometry) was carried out on hematoxylin and eosin-stained sections from 24 radical prostatectomy specimens with high-grade PIN (12 with flat and 12 with cribriform architectural pattern, respectively) and cancer. Quantification was also conducted on the normal looking secretory epithelium. Discriminant analysis and the nonsupervised learning algorithm P-index were used to identify suitable subsets of features useful for the discrimination and classification of pathological groups and to explore multivariate data structure in the pathological subgroups. The average nuclear abnormality increases monotonically from the histologically normal appearing secretory epithelium to high-grade PIN and to adenocarcinoma. The nuclei from the so-called perimeter compartment of the flat high-grade PIN lesions show a higher nuclear abnormality compared to the nuclei of the cribriform high-grade PINs. Discriminant analysis shows that flat and cribriform high-grade PINs fall into two populations. Processing by the nonsupervised learning algorithm P-index revealed the existence of three well-defined, distinct subpopulations of nuclei of different chromatin phenotype. In the flat high-grade PIN lesions the proportions of nuclei in the three subpopulations are 16.5% (low abnormality), 25.0% (mid abnormality) and 58.5% (high abnormality), respectively. In the cribriform high-grade PIN lesions, 100% of the nuclei are in the mid-abnormality subpopulation. These differences are also discernible in the co-occurring adenocarcinoma and the histologically normal appearing secretory epithelium. To conclude, karyometry and statistical analysis detect the existence of distinct cell subpopulations of different chromatin

  9. Urban architecture in urban renewal

    DEFF Research Database (Denmark)

    Holmgren, Steen; Svensson, Ole

    2001-01-01

    and without obvious architectural value. These issues raise pertinent questions: what urban architectural problems and qualities exist in the complex, inner suburbs? What differences exist between professionals' and residents' perceptions and assessments of urban architecture? How can a shared language...

  10. Modulation of chromatin structure by the FACT histone chaperone complex regulates HIV-1 integration.

    Science.gov (United States)

    Matysiak, Julien; Lesbats, Paul; Mauro, Eric; Lapaillerie, Delphine; Dupuy, Jean-William; Lopez, Angelica P; Benleulmi, Mohamed Salah; Calmels, Christina; Andreola, Marie-Line; Ruff, Marc; Llano, Manuel; Delelis, Olivier; Lavigne, Marc; Parissi, Vincent

    2017-07-28

    Insertion of retroviral genome DNA occurs in the chromatin of the host cell. This step is modulated by chromatin structure as nucleosomes compaction was shown to prevent HIV-1 integration and chromatin remodeling has been reported to affect integration efficiency. LEDGF/p75-mediated targeting of the integration complex toward RNA polymerase II (polII) transcribed regions ensures optimal access to dynamic regions that are suitable for integration. Consequently, we have investigated the involvement of polII-associated factors in the regulation of HIV-1 integration. Using a pull down approach coupled with mass spectrometry, we have selected the FACT (FAcilitates Chromatin Transcription) complex as a new potential cofactor of HIV-1 integration. FACT is a histone chaperone complex associated with the polII transcription machinery and recently shown to bind LEDGF/p75. We report here that a tripartite complex can be formed between HIV-1 integrase, LEDGF/p75 and FACT in vitro and in cells. Biochemical analyzes show that FACT-dependent nucleosome disassembly promotes HIV-1 integration into chromatinized templates, and generates highly favored nucleosomal structures in vitro. This effect was found to be amplified by LEDGF/p75. Promotion of this FACT-mediated chromatin remodeling in cells both increases chromatin accessibility and stimulates HIV-1 infectivity and integration. Altogether, our data indicate that FACT regulates HIV-1 integration by inducing local nucleosomes dissociation that modulates the functional association between the incoming intasome and the targeted nucleosome.

  11. Non coding RNA: sequence-specific guide for chromatin modification and DNA damage signaling

    Directory of Open Access Journals (Sweden)

    Sofia eFrancia

    2015-11-01

    Full Text Available Chromatin conformation shapes the environment in which our genome is transcribed into RNA. Transcription is a source of DNA damage, thus it often occurs concomitantly to DNA damage signaling. Growing amounts of evidence suggest that different types of RNAs can, independently from their protein-coding properties, directly affect chromatin conformation, transcription and splicing, as well as promote the activation of the DNA damage response (DDR and DNA repair. Therefore, transcription paradoxically functions to both threaten and safeguard genome integrity. On the other hand, DNA damage signaling is known to modulate chromatin to suppress transcription of the surrounding genetic unit. It is thus intriguing to understand how transcription can modulate DDR signaling while, in turn, DDR signaling represses transcription of chromatin around the DNA lesion. An unexpected player in this field is the RNA interference (RNAi machinery, which play roles in transcription, splicing and chromatin modulation in several organisms. Non-coding RNAs (ncRNAs and several protein factors involved in the RNAi pathway are well known master regulators of chromatin while only recent reports suggest that ncRNAs are involved in DDR signaling and homology-mediated DNA repair. Here, we discuss the experimental evidence supporting the idea that ncRNAs act at the genomic loci from which they are transcribed to modulate chromatin, DDR signaling and DNA repair.

  12. Large-scale Comparative Study of Hi-C-based Chromatin 3D Structure Modeling Methods

    KAUST Repository

    Wang, Cheng

    2018-05-17

    Chromatin is a complex polymer molecule in eukaryotic cells, primarily consisting of DNA and histones. Many works have shown that the 3D folding of chromatin structure plays an important role in DNA expression. The recently proposed Chro- mosome Conformation Capture technologies, especially the Hi-C assays, provide us an opportunity to study how the 3D structures of the chromatin are organized. Based on the data from Hi-C experiments, many chromatin 3D structure modeling methods have been proposed. However, there is limited ground truth to validate these methods and no robust chromatin structure alignment algorithms to evaluate the performance of these methods. In our work, we first made a thorough literature review of 25 publicly available population Hi-C-based chromatin 3D structure modeling methods. Furthermore, to evaluate and to compare the performance of these methods, we proposed a novel data simulation method, which combined the population Hi-C data and single-cell Hi-C data without ad hoc parameters. Also, we designed a global and a local alignment algorithms to measure the similarity between the templates and the chromatin struc- tures predicted by different modeling methods. Finally, the results from large-scale comparative tests indicated that our alignment algorithms significantly outperform the algorithms in literature.

  13. The effect of higher order chromatin structure on DNA damage and repair

    International Nuclear Information System (INIS)

    Yasui, L.S.; Warters, R.L.; Higashikubo, R.

    1985-01-01

    Alterations in chromatin structure are thought to play an important role in various radiobiological end points, i.e., DNA damage, DNA damage repair and cell survival. The authors use here the isoleucine deprivation technique to decondense higher order chromatin structure and asses X-ray induced DNA damage, DNA damage repair and cell survival on cells with decondensed chromatin as compared to controls. This chromatin decondensation manifests itself as a 30 fold decrease in nuclear area occupied by heterochromatin, an increased rate of Micrococcal nuclease digestion, 15% increased ethidium bromide intercalation and an altered binding capacity of Hl histone. These chromatin/nuclear changes do not affect X-ray induced DNA damage as measured by the alkaline elution technique or cell survival but slows DNA damage repair by 2 fold. Therefore, even though the chromatin appears more accessible to DNA damage and repair processes, these particular nuclear changes do not affect the DNA damaging effects of X-rays and in addition, repair is not enhanced by the ''relaxed'' state of chromatin. It is proposed that the altered metabolic state of isoleucine deprived cells provides a less efficient system for the repair of X-ray induced DNA damage

  14. [Automated morphometric evaluation of the chromatin structure of liver cell nuclei after vagotomy].

    Science.gov (United States)

    Butusova, N N; Zhukotskiĭ, A V; Sherbo, I V; Gribkov, E N; Dubovaia, T K

    1989-05-01

    The morphometric analysis of the interphase chromatine structure of the hepatic cells nuclei was carried out on the automated TV installation for the quantitative analysis of images "IBAS-2" (by the OPTON firm, the FRG) according to 50 optical and geometric parameters during various periods (1.2 and 4 weeks) after the vagotomy operation. It is determined that upper-molecular organisation of chromatine undergoes the biggest changes one week after operation, and changes of granular component are more informative than changes of the nongranular component (with the difference 15-20%). It was also revealed that chromatine components differ in tinctorial properties, which are evidently dependent on physicochemical characteristics of the chromatine under various functional conditions of the cell. As a result of the correlation analysis the group of morphometric indices of chromatine structure was revealed, which are highly correlated with level of transcription activity of chromatine during various terms after denervation. The correlation quotient of these parameters is 0.85-0.97. The summing up: vagus denervation of the liver causes changes in the morphofunctional organisation of the chromatine.

  15. [Comparative investigation of the non-histone proteins of chromatin from pigeon erythroblasts and erythrocytes].

    Science.gov (United States)

    Fedina, A B; Gazarian, G G

    1976-01-01

    Chromosomal non-histone proteins are obtained from nuclei of two types of pigeon erythroid cells: erythroblasts (cells active in RNA synthesis) and erythrocytes (cells with repressed RNA synthesis). They are well soluble in solutions of low ionic strength. Electrophoretic separation of the obtained non-histone proteins in polyacrylamide gels with urea and SDS shows the presence of qualitative differences in the pattern of non-histone proteins of chromatine from erythroblasts and erythrocytes. By electrophoresis in urea some protein bands of non-histone proteins of chromatine from erythroblasts were found which disappear with the aging of cells. At the same time two protein fractions were observed in chromatine from erythrocytes which were absent in that of erythroblasts. Disappearance of some high molecular weight protein fractions from erythrocyte chromatine as compared to erythroblasts was observed by separation of the non-histone proteins in the presence of SDS. These fractions of the non-histone proteins disappearing during aging of cells are well extractable from erythroblast chromatine by 0.35 M NaCl solution. In the in vitro system with E. coli RNA polymerase addition of non-histone proteins of chromatine from erythroblasts to chromatine from erythrocytes increases RNA synthesis 2--3 times. At the same time addition of non-histone proteins from erythrocytes is either without any influence on this process or somewhat inhibiting.

  16. Travels in Architectural History

    Directory of Open Access Journals (Sweden)

    Davide Deriu

    2016-11-01

    Full Text Available Travel is a powerful force in shaping the perception of the modern world and plays an ever-growing role within architectural and urban cultures. Inextricably linked to political and ideological issues, travel redefines places and landscapes through new transport infrastructures and buildings. Architecture, in turn, is reconstructed through visual and textual narratives produced by scores of modern travellers — including writers and artists along with architects themselves. In the age of the camera, travel is bound up with new kinds of imaginaries; private records and recollections often mingle with official, stereotyped views, as the value of architectural heritage increasingly rests on the mechanical reproduction of its images. Whilst students often learn about architectural history through image collections, the place of the journey in the formation of the architect itself shifts. No longer a lone and passionate antiquarian or an itinerant designer, the modern architect eagerly hops on buses, trains, and planes in pursuit of personal as well as professional interests. Increasingly built on a presumption of mobility, architectural culture integrates travel into cultural debates and design experiments. By addressing such issues from a variety of perspectives, this collection, a special 'Architectural Histories' issue on travel, prompts us to rethink the mobile conditions in which architecture has historically been produced and received.

  17. On Detailing in Contemporary Architecture

    DEFF Research Database (Denmark)

    Kristensen, Claus; Kirkegaard, Poul Henning

    2010-01-01

    Details in architecture have a significant influence on how architecture is experienced. One can touch the materials and analyse the detailing - thus details give valuable information about the architectural scheme as a whole. The absence of perceptual stimulation like details and materiality...... / tactility can blur the meaning of the architecture and turn it into an empty statement. The present paper will outline detailing in contemporary architecture and discuss the issue with respect to architectural quality. Architectural cases considered as sublime piece of architecture will be presented...

  18. Fractionated Spacecraft Architectures Seeding Study

    National Research Council Canada - National Science Library

    Mathieu, Charlotte; Weigel, Annalisa

    2006-01-01

    .... Models were developed from a customer-centric perspective to assess different fractionated spacecraft architectures relative to traditional spacecraft architectures using multi-attribute analysis...

  19. High-resolution mapping reveals links of HP1 with active and inactive chromatin components.

    Directory of Open Access Journals (Sweden)

    Elzo de Wit

    2007-03-01

    Full Text Available Heterochromatin protein 1 (HP1 is commonly seen as a key factor of repressive heterochromatin, even though a few genes are known to require HP1-chromatin for their expression. To obtain insight into the targeting of HP1 and its interplay with other chromatin components, we have mapped HP1-binding sites on Chromosomes 2 and 4 in Drosophila Kc cells using high-density oligonucleotide arrays and the DNA adenine methyltransferase identification (DamID technique. The resulting high-resolution maps show that HP1 forms large domains in pericentric regions, but is targeted to single genes on chromosome arms. Intriguingly, HP1 shows a striking preference for exon-dense genes on chromosome arms. Furthermore, HP1 binds along entire transcription units, except for 5' regions. Comparison with expression data shows that most of these genes are actively transcribed. HP1 target genes are also marked by the histone variant H3.3 and dimethylated histone 3 lysine 4 (H3K4me2, which are both typical of active chromatin. Interestingly, H3.3 deposition, which is usually observed along entire transcription units, is limited to the 5' ends of HP1-bound genes. Thus, H3.3 and HP1 are mutually exclusive marks on active chromatin. Additionally, we observed that HP1-chromatin and Polycomb-chromatin are nonoverlapping, but often closely juxtaposed, suggesting an interplay between both types of chromatin. These results demonstrate that HP1-chromatin is transcriptionally active and has extensive links with several other chromatin components.

  20. A Damage-Independent Role for 53BP1 that Impacts Break Order and Igh Architecture during Class Switch Recombination

    Directory of Open Access Journals (Sweden)

    Pedro P. Rocha

    2016-06-01

    Full Text Available During class switch recombination (CSR, B cells replace the Igh Cμ or δ exons with another downstream constant region exon (CH, altering the antibody isotype. CSR occurs through the introduction of AID-mediated double-strand breaks (DSBs in switch regions and subsequent ligation of broken ends. Here, we developed an assay to investigate the dynamics of DSB formation in individual cells. We demonstrate that the upstream switch region Sμ is first targeted during recombination and that the mechanism underlying this control relies on 53BP1. Surprisingly, regulation of break order occurs through residual binding of 53BP1 to chromatin before the introduction of damage and independent of its established role in DNA repair. Using chromosome conformation capture, we show that 53BP1 mediates changes in chromatin architecture that affect break order. Finally, our results explain how changes in Igh architecture in the absence of 53BP1 could promote inversional rearrangements that compromise CSR.

  1. Architectural Knitted Surfaces

    DEFF Research Database (Denmark)

    Mossé, Aurélie

    2010-01-01

    WGSN reports from the Architectural Knitted Surfaces workshop recently held at ShenkarCollege of Engineering and Design, Tel Aviv, which offered a cutting-edge insight into interactive knitted surfaces. With the increasing role of smart textiles in architecture, the Architectural Knitted Surfaces...... workshop brought together architects and interior and textile designers to highlight recent developments in intelligent knitting. The five-day workshop was led by architects Ayelet Karmon and Mette Ramsgaard Thomsen, together with Amir Cang and Eyal Sheffer from the Knitting Laboratory, in collaboration...

  2. Towards Adaptive Evolutionary Architecture

    DEFF Research Database (Denmark)

    Bak, Sebastian HOlt; Rask, Nina; Risi, Sebastian

    2016-01-01

    This paper presents first results from an interdisciplinary project, in which the fields of architecture, philosophy and artificial life are combined to explore possible futures of architecture. Through an interactive evolutionary installation, called EvoCurtain, we investigate aspects of how...... to the development of designs tailored to the individual preferences of inhabitants, changing the roles of architects and designers entirely. Architecture-as-it-could-be is a philosophical approach conducted through artistic methods to anticipate the technological futures of human-centered development within...

  3. Computer architecture technology trends

    CERN Document Server

    1991-01-01

    Please note this is a Short Discount publication. This year's edition of Computer Architecture Technology Trends analyses the trends which are taking place in the architecture of computing systems today. Due to the sheer number of different applications to which computers are being applied, there seems no end to the different adoptions which proliferate. There are, however, some underlying trends which appear. Decision makers should be aware of these trends when specifying architectures, particularly for future applications. This report is fully revised and updated and provides insight in

  4. A new and improved algorithm for the quantification of chromatin condensation from microscopic data shows decreased chromatin condensation in regenerating axolotl limb cells.

    Directory of Open Access Journals (Sweden)

    Julian Sosnik

    Full Text Available The nuclear landscape plays an important role in the regulation of tissue and positional specific genes in embryonic and developing cells. Changes in this landscape can be dynamic, and are associated with the differentiation of cells during embryogenesis, and the de-differentiation of cells during induced pluripotent stem cell (iPSC formation and in many cancers. However, tools to quantitatively characterize these changes are limited, especially in the in vivo context, where numerous tissue types are present and cells are arranged in multiple layers. Previous tools have been optimized for the monolayer nature of cultured cells. Therefore, we present a new algorithm to quantify the condensation of chromatin in two in vivo systems. We first developed this algorithm to quantify changes in chromatin compaction and validated it in differentiating spermatids in zebrafish testes. Our algorithm successfully detected the typical increase in chromatin compaction as these cells differentiate. We then employed the algorithm to quantify the changes that occur in amphibian limb cells as they participate in a regenerative response. We observed that the chromatin in the limb cells de-compacts as they contribute to the regenerating organ. We present this new tool as an open sourced software that can be readily accessed and optimized to quantify chromatin compaction in complex multi-layered samples.

  5. Structural hierarchy of chromatin in chicken erythrocyte nuclei based on small-angle neutron scattering: Fractal nature of the large-scale chromatin organization

    International Nuclear Information System (INIS)

    Lebedev, D. V.; Filatov, M. V.; Kuklin, A. I.; Islamov, A. Kh.; Stellbrink, J.; Pantina, R. A.; Denisov, Yu. Yu.; Toperverg, B. P.; Isaev-Ivanov, V. V.

    2008-01-01

    The chromatin organization in chicken erythrocyte nuclei was studied by small-angle neutron scattering in the scattering-vector range from 1.5 x 10 -1 to 10 -4 A -1 with the use of the contrast-variation technique. This scattering-vector range corresponds to linear dimensions from 4 nm to 6 μm and covers the whole hierarchy of chromatin structures, from the nucleosomal structure to the entire nucleus. The results of the present study allowed the following conclusions to be drawn: (1) both the chromatin-protein structure and the structure of the nucleic acid component in chicken erythrocyte nuclei have mass-fractal properties, (2) the structure of the protein component of chromatin exhibits a fractal behavior on scales extending over two orders of magnitude, from the nucleosomal size to the size of an entire nucleus, and (3) the structure of the nucleic acid component of chromatin in chicken erythrocyte nuclei is likewise of a fractal nature and has two levels of organization or two phases with the crossover point at about 300-400 nm

  6. Effect of radiation and alkylating agents on chromatin degradation in normal and malignant lymphoid cells

    International Nuclear Information System (INIS)

    Ryabchenko, N.I.; Yurashkova, V.; Ivannik, B.P.; Konov, A.V.; Drashil, V.

    1991-01-01

    Regularities of chromatin degradation in thymocytes and LS/BL tumor cells have been investigated. It has been shown that the rate of DNA degradation by Ca/Mg-dependent endonuclease in LS/BL tumor cells is 25 times lower than that in thymocytes, and radiation does not induce chormatin degradation. The alkylating agent TS 160 causes chromatin degradation in both LS/Bl cells and thymocytes. In contrast to radiation TS 160 inhibits the endogenous chromatin degradation by Ca/Mg-dependent endonuclease in thymocytes

  7. The global relationship between chromatin physical topology, fractal structure, and gene expression

    DEFF Research Database (Denmark)

    Almassalha, Luay M; Tiwari, A; Ruhoff, P T

    2017-01-01

    in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D...... show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating...

  8. Vitamin D receptor (VDR) promoter targeting through a novel chromatin remodeling complex.

    Science.gov (United States)

    Kato, Shigeaki; Fujiki, Ryoji; Kitagawa, Hirochika

    2004-05-01

    We have purified nuclear complexes for Vitamin D receptor (VDR), and identified one of them as a novel ATP-dependent chromatine remodeling containing Williams syndrome transcription factor (WSTF), that is supposed to be responsible for Williams syndrome. This complex (WSTF including nucleosome assembly complex (WINAC)) exhibited an ATP-dependent chromatin remodeling activity in vitro. Transient expression assays revealed that WINAC potentiates ligand-induced function of VDR in gene activation and repression. Thus, this study describes a molecular basis of the VDR function on chromosomal DNA through chromatine remodeling.

  9. Excision of x-ray-induced thymine damage in chromatin from heated cells

    International Nuclear Information System (INIS)

    Warters, R.L.; Roti Roti, J.L.

    1979-01-01

    Experiments were performed to distinguish between two possible modes of hyperthermia-induced inhibition of thymine base damage excision from the DNA of CHO cells: (1) heat denaturation of excision enzyme(s) or (2) heat-induced alteration of the substrate for damage excision (chromatin). While hyperthermia (45 0 C, 15 min) had no apparent effect on the capacity of the excision enzymes to excise damage from DNA it had a dramatic effect (ca. 80% inhibition) on the ability of chromatin to serve as a substrate for unheated enzymes. These results suggest that hyperthermia-induced radiosensitization of CHO cells may be due primarily to lesions in the cellular chromatin

  10. 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

    hypersensitive site analysis to investigate the genome-wide changes in chromatin structure that accompany the binding of adipogenic transcription factors. These analyses revealed a dramatic and dynamic modulation of the chromatin landscape during the first hours of adipocyte differentiation that coincides...... 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...

  11. Phosphorylation of both nucleoplasmin domains is required for activation of its chromatin decondensation activity

    DEFF Research Database (Denmark)

    Bañuelos, Sonia; Omaetxebarria, Miren J; Ramos, Isbaal

    2007-01-01

    Nucleoplasmin (NP) is a histone chaperone involved in nucleosome assembly, chromatin decondensation at fertilization, and apoptosis. To carry out these activities NP has to interact with different types of histones, an interaction that is regulated by phosphorylation. Here we have identified...... are found at the tail domain, flanking the nuclear localization signal. Phosphorylation-mimicking mutations render a recombinant protein as active in chromatin decondensation as hyperphosphorylated NP isolated from Xenopus laevis eggs. Comparison of mutants in which the core and tail domains of the protein...... were independently or simultaneously "activated" indicates that activation or phosphorylation of both protein domains is required for NP to efficiently extract linker-type histones from chromatin....

  12. Early aberrations in chromatin dynamics in embryos produced under In vitro conditions

    DEFF Research Database (Denmark)

    Deshmukh, Rahul Shahaji; Østrup, Olga; Strejcek, Frantisek

    2012-01-01

    standard to that of embryos produced by IVF, parthenogenetic activation (PA), or SCNT. In contrast to IV embryos, chromatin spatial and temporal dynamics in PA, IVF, and SCNT embryos were altered; starting with aberrant chromatin-nuclear envelope interactions at the two-cell stage, delayed chromatin...... decondensation and nucleolar development at the four-cell stage, and ultimately culminating in failure of proper first lineage segregation at the blastocyst stage, demonstrated by poorly defined inner cell mass. Interestingly, in vitro produced (IVP) embryos also lacked a heterochromatin halo around nucleolar...

  13. Architectures of prototypes and architectural prototyping

    DEFF Research Database (Denmark)

    Hansen, Klaus Marius; Christensen, Michael; Sandvad, Elmer

    1998-01-01

    together as a team, but developed a prototype that more than fulfilled the expectations of the shipping company. The prototype should: - complete the first major phase within 10 weeks, - be highly vertical illustrating future work practice, - continuously live up to new requirements from prototyping......This paper reports from experience obtained through development of a prototype of a global customer service system in a project involving a large shipping company and a university research group. The research group had no previous knowledge of the complex business of shipping and had never worked...... sessions with users, - evolve over a long period of time to contain more functionality - allow for 6-7 developers working intensively in parallel. Explicit focus on the software architecture and letting the architecture evolve with the prototype played a major role in resolving these conflicting...

  14. Analysis of Architecture Pattern Usage in Legacy System Architecture Documentation

    NARCIS (Netherlands)

    Harrison, Neil B.; Avgeriou, Paris

    2008-01-01

    Architecture patterns are an important tool in architectural design. However, while many architecture patterns have been identified, there is little in-depth understanding of their actual use in software architectures. For instance, there is no overview of how many patterns are used per system or

  15. Bionics in architecture

    Directory of Open Access Journals (Sweden)

    Sugár Viktória

    2017-04-01

    Full Text Available The adaptation of the forms and phenomena of nature is not a recent concept. Observation of natural mechanisms has been a primary source of innovation since prehistoric ages, which can be perceived through the history of architecture. Currently, this idea is coming to the front again through sustainable architecture and adaptive design. Investigating natural innovations and the clear-outness of evolution during the 20th century led to the creation of a separate scientific discipline, Bionics. Architecture and Bionics are strongly related to each other, since the act of building is as old as the human civilization - moreover its first formal and structural source was obviously the surrounding environment. Present paper discusses the definition of Bionics and its connection with the architecture.

  16. DSP Architecture Design Essentials

    CERN Document Server

    Marković, Dejan

    2012-01-01

    In DSP Architecture Design Essentials, authors Dejan Marković and Robert W. Brodersen cover a key subject for the successful realization of DSP algorithms for communications, multimedia, and healthcare applications. The book addresses the need for DSP architecture design that maps advanced DSP algorithms to hardware in the most power- and area-efficient way. The key feature of this text is a design methodology based on a high-level design model that leads to hardware implementation with minimum power and area. The methodology includes algorithm-level considerations such as automated word-length reduction and intrinsic data properties that can be leveraged to reduce hardware complexity. From a high-level data-flow graph model, an architecture exploration methodology based on linear programming is used to create an array of architectural solutions tailored to the underlying hardware technology. The book is supplemented with online material: bibliography, design examples, CAD tutorials and custom software.

  17. METRIC context unit architecture

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, R.O.

    1988-01-01

    METRIC is an architecture for a simple but powerful Reduced Instruction Set Computer (RISC). Its speed comes from the simultaneous processing of several instruction streams, with instructions from the various streams being dispatched into METRIC's execution pipeline as they become available for execution. The pipeline is thus kept full, with a mix of instructions for several contexts in execution at the same time. True parallel programming is supported within a single execution unit, the METRIC Context Unit. METRIC's architecture provides for expansion through the addition of multiple Context Units and of specialized Functional Units. The architecture thus spans a range of size and performance from a single-chip microcomputer up through large and powerful multiprocessors. This research concentrates on the specification of the METRIC Context Unit at the architectural level. Performance tradeoffs made during METRIC's design are discussed, and projections of METRIC's performance are made based on simulation studies.

  18. Flexible weapons architecture design

    Science.gov (United States)

    Pyant, William C., III

    Present day air-delivered weapons are of a closed architecture, with little to no ability to tailor the weapon for the individual engagement. The closed architectures require weaponeers to make the target fit the weapon instead of fitting the individual weapons to a target. The concept of a flexible weapons aims to modularize weapons design using an open architecture shell into which different modules are inserted to achieve the desired target fractional damage while reducing cost and civilian casualties. This thesis shows that the architecture design factors of damage mechanism, fusing, weapons weight, guidance, and propulsion are significant in enhancing weapon performance objectives, and would benefit from modularization. Additionally, this thesis constructs an algorithm that can be used to design a weapon set for a particular target class based on these modular components.

  19. Border information flow architecture

    Science.gov (United States)

    2006-04-01

    This brochure describes the Border Information Flow Architecture (BIFA). The Transportation Border Working Group, a bi-national group that works to enhance coordination and planning between the United States and Canada, identified collaboration on th...

  20. Layered Fault Management Architecture

    National Research Council Canada - National Science Library

    Sztipanovits, Janos

    2004-01-01

    ... UAVs or Organic Air Vehicles. The approach of this effort was to analyze fault management requirements of formation flight for fleets of UAVs, and develop a layered fault management architecture which demonstrates significant...

  1. Thermal Space in Architecture

    DEFF Research Database (Denmark)

    Petersen, Mads Dines

    Present research is revolving around the design process and the use of digital applications to support the design process among architects. This work is made in relation to the current discussions about sustainable architecture and the increased focus on energy consumption and the comfort in our...... and understanding of spaces in buildings can change significantly and instead of the creation of frozen geometrical spaces, thermal spaces can be created as it is suggested in meteorological architecture where functions are distributed in relation to temperature gradients. This creates an interesting contrast......-introducing an increased adaptability in the architecture can be a part of re-defining the environmental agenda and re-establish a link between the environment of the site and the environment of the architecture and through that an increased appreciation of the sensuous space here framed in discussions about thermal...

  2. The toolbus coordination architecture

    NARCIS (Netherlands)

    Bergstra, J.A.; Klint, P.

    1996-01-01

    Building large, heterogeneous, distributed software systems poses serious problems for the software engineer; achieving interoperability of software systems is still a major challenge. We describe an experiment in designing a generic software architecture for solving these problems. To get

  3. Service Modularity and Architecture

    DEFF Research Database (Denmark)

    Brax, Saara A.; Bask, Anu; Hsuan, Juliana

    2017-01-01

    , platform-based and mass-customized service business models, comparative research designs, customer perspectives and service experience, performance in context of modular services, empirical evidence of benefits and challenges, architectural innovation in services, modularization in multi-provider contexts......Purpose: Services are highly important in a world economy which has increasingly become service driven. There is a growing need to better understand the possibilities for, and requirements of, designing modular service architectures. The purpose of this paper is to elaborate on the roots...... of the emerging research stream on service modularity, provide a concise overview of existing work on the subject, and outline an agenda for future research on service modularity and architecture. The articles in the special issue offer four diverse sets of research on service modularity and architecture. Design...

  4. Models in architectural design

    OpenAIRE

    Pauwels, Pieter

    2017-01-01

    Whereas architects and construction specialists used to rely mainly on sketches and physical models as representations of their own cognitive design models, they rely now more and more on computer models. Parametric models, generative models, as-built models, building information models (BIM), and so forth, they are used daily by any practitioner in architectural design and construction. Although processes of abstraction and the actual architectural model-based reasoning itself of course rema...

  5. Artificial cognition architectures

    CERN Document Server

    Crowder, James A; Friess, Shelli A

    2013-01-01

    The goal of this book is to establish the foundation, principles, theory, and concepts that are the backbone of real, autonomous Artificial Intelligence. Presented here are some basic human intelligence concepts framed for Artificial Intelligence systems. These include concepts like Metacognition and Metamemory, along with architectural constructs for Artificial Intelligence versions of human brain functions like the prefrontal cortex. Also presented are possible hardware and software architectures that lend themselves to learning, reasoning, and self-evolution

  6. Religious Architecture : Anthropological Perspectives

    OpenAIRE

    2013-01-01

    Religious Architecture: Anthropological Perspectives develops an anthropological perspective on modern religious architecture, including mosques, churches and synagogues. Borrowing from a range of theoretical perspectives on space-making and material religion, this volume looks at how religious buildings take their place in opposition to the secular surroundings, how they, as evocations of the sublime, help believers to move beyond the boundaries of modern subjectivity, and how they, in their...

  7. Climate and architecture

    DEFF Research Database (Denmark)

    Tind Kristensen, Eva; Friis Møller, Winnie; Rotne, Georg

    Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder.......Climate and Architecture analyserer klimaets rolle i arkitekturen. Intentionen med bogen er at pege på nogle af de mange muligheder for bygningers klimaregulering, som et mere detaljeret studie af de lokale klimatiske forhold og den stedlige byggeskik tilbyder....

  8. Greek architecture now

    DEFF Research Database (Denmark)

    Skousbøll, Karin Merete

    2006-01-01

    With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas.......With the author's Scandinavian viewpoint the aim of this book has been an investigation into contemporary Greek architecture and at the same time providing an understanding for its essential characteristics based on the historic, cultural heritage of Hellas....

  9. Essential software architecture

    CERN Document Server

    Gorton, Ian

    2011-01-01

    Job titles like ""Technical Architect"" and ""Chief Architect"" nowadays abound in software industry, yet many people suspect that ""architecture"" is one of the most overused and least understood terms in professional software development. Gorton's book tries to resolve this dilemma. It concisely describes the essential elements of knowledge and key skills required to be a software architect. The explanations encompass the essentials of architecture thinking, practices, and supporting technologies. They range from a general understanding of structure and quality attributes through technical i

  10. Relocalization of human chromatin remodeling cofactor TIP48 in mitosis

    International Nuclear Information System (INIS)

    Sigala, Barbara; Edwards, Mina; Puri, Teena; Tsaneva, Irina R.

    2005-01-01

    TIP48 is a highly conserved eukaryotic AAA + protein which is an essential cofactor for several complexes involved in chromatin acetylation and remodeling, transcriptional and developmental regulation and nucleolar organization and trafficking. We show that TIP48 abundance in HeLa cells did not change during the cell cycle, nor did its distribution in various biochemical fractions. However, we observed distinct changes in the subcellular localization of TIP48 during M phase using immunofluorescence microscopy. Our studies demonstrate that in interphase cells TIP48 was found mainly in the nucleus and exhibited a distinct localization in the nuclear periphery. As the cells entered mitosis, TIP48 was excluded from the condensing chromosomes but showed association with the mitotic apparatus. During anaphase, some TIP48 was detected in the centrosome colocalizing with tubulin but the strongest staining appeared in the mitotic equator associated with the midzone central spindle. Accumulation of TIP48 in the midzone and the midbody was observed in late telophase and cytokinesis. This redeployment of TIP48 during anaphase and cytokinesis was independent of microtubule assembly. The relocation of endogenous TIP48 to the midzone/midbody under physiological conditions suggests a novel and distinct function for TIP48 in mitosis and possible involvement in the exit of mitosis

  11. Sulforaphane Modifies Histone H3, Unpacks Chromatin, and Primes Defense.

    Science.gov (United States)

    Schillheim, Britta; Jansen, Irina; Baum, Stephani; Beesley, Alexander; Bolm, Carsten; Conrath, Uwe

    2018-03-01

    Modern crop production calls for agrochemicals that prime plants for enhanced defense. Reliable test systems for spotting priming-inducing chemistry, however, are rare. We developed an assay for the high-throughput search for compounds that prime microbial pattern-induced secretion of antimicrobial furanocoumarins (phytoalexins) in cultured parsley cells. The screen produced 1-isothiocyanato-4-methylsulfinylbutane (sulforaphane; SFN), a secondary metabolite in many crucifers, as a novel defense priming compound. While elucidating SFN's mode of action in defense priming, we found that in Arabidopsis ( Arabidopsis thaliana ) the isothiocyanate provokes covalent modification (K4me3, K9ac) of histone H3 in the promoter and promoter-proximal region of defense genes WRKY6 and PDF1 2 , but not PR1 SFN-triggered H3K4me3 and H3K9ac coincide with chromatin unpacking in the WRKY6 and PDF1 2 regulatory regions, primed WRKY6 expression, unprimed PDF1 2 activation, and reduced susceptibility to downy mildew disease ( Hyaloperonospora arabidopsidis ). Because SFN also directly inhibits H arabidopsidis and other plant pathogens, the isothiocyanate is promising for the development of a plant protectant with a dual mode of action. © 2018 American Society of Plant Biologists. All Rights Reserved.

  12. Adenovirus chromatin structure at different stages of infection

    Energy Technology Data Exchange (ETDEWEB)

    Daniell, E.; Groff, D.E.; Fedor, M.J.

    1981-12-01

    The authors investigated the structure of adenovirus deoxyribonecleic acid (DNA)-protein complexes in nuclei of infected cells by using micrococal nuclease. Parental (infecting) DNA was digested into multimers which had a unit fragment size that was indistinguishable from the size of the nucleosomal repeat of cellular chromatin. This pattern was maintained in parental DNA throughout infection. Similar repeating units were detected in hamster cells that were nonpermissive for human adenovirus and in cells pretreated with n-butyrate. Late in infection, the pattern of digestion of viral DNA was determined by two different experimental approaches. Nuclear DNA was electrophoresed, blotted, and hybridized with labeled viral sequences; in this procedure all virus-specific DNA was detected. This technique revealed a diffuse protected band of viral DNA that was smaller than 160 base pairs, but no discrete multimers. All regions of the genome were represented in the protected DNA. To examine the nuclease protection of newly replicated viral DNA, infected cells were labeled with (/sup 3/)thymidine after blocking of cellular DNA synthesis but not viral DNA synthesis. With this procedure they identified a repeating unit which was distinctly different from the cellular nucleosomal repeat. The authors found broad bands with midpoints at 200, 400, and 600 base pairs, as well as the limit digest material revealed by blotting. High-resolution acrylamide gel electrophoresis revealed that the viral species comprised a series of closely spaced bands ranging in size from less than 30 to 250 base pairs.

  13. ENCODE: A Sourcebook of Epigenomes and Chromatin Language

    Directory of Open Access Journals (Sweden)

    Maryam Yavartanoo

    2013-03-01

    Full Text Available Until recently, since the Human Genome Project, the general view has been that the majority of the human genome is composed of junk DNA and has little or no selective advantage to the organism. Now we know that this conclusion is an oversimplification. In April 2003, the National Human Genome Research Institute (NHGRI launched an international research consortium called Encyclopedia of DNA Elements (ENCODE to uncover non-coding functional elements in the human genome. The result of this project has identified a set of new DNA regulatory elements, based on novel relationships among chromatin accessibility, histone modifications, nucleosome positioning, DNA methylation, transcription, and the occupancy of sequence-specific factors. The project gives us new insights into the organization and regulation of the human genome and epigenome. Here, we sought to summarize particular aspects of the ENCODE project and highlight the features and data that have recently been released. At the end of this review, we have summarized a case study we conducted using the ENCODE epigenome data.

  14. Two independent modes of chromatin organization revealed by cohesin removal.

    Science.gov (United States)

    Schwarzer, Wibke; Abdennur, Nezar; Goloborodko, Anton; Pekowska, Aleksandra; Fudenberg, Geoffrey; Loe-Mie, Yann; Fonseca, Nuno A; Huber, Wolfgang; H Haering, Christian; Mirny, Leonid; Spitz, Francois

    2017-11-02

    Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

  15. Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast fbp1.

    Science.gov (United States)

    Adachi, Akira; Senmatsu, Satoshi; Asada, Ryuta; Abe, Takuya; Hoffman, Charles S; Ohta, Kunihiro; Hirota, Kouji

    2018-05-03

    Numerous noncoding RNA transcripts are detected in eukaryotic cells. Noncoding RNAs transcribed across gene promoters are involved in the regulation of mRNA transcription via chromatin modulation. This function of noncoding RNA transcription was first demonstrated for the fission yeast fbp1 gene, where a cascade of noncoding RNA transcription events induces chromatin remodeling to facilitate transcription factor binding. We recently demonstrated that the noncoding RNAs from the fbp1 upstream region facilitate binding of the transcription activator Atf1 and thereby promote histone acetylation. Histone acetylation by histone acetyl transferases (HATs) and ATP-dependent chromatin remodelers (ADCRs) are implicated in chromatin remodeling, but the interplay between HATs and ADCRs in this process has not been fully elucidated. Here, we examine the roles played by two distinct ADCRs, Snf22 and Hrp3, and by the HAT Gcn5 in the transcriptional activation of fbp1. Snf22 and Hrp3 redundantly promote disassembly of chromatin in the fbp1 upstream region. Gcn5 critically contributes to nucleosome eviction in the absence of either Snf22 or Hrp3, presumably by recruiting Hrp3 in snf22∆ cells and Snf22 in hrp3∆ cells. Conversely, Gcn5-dependent histone H3 acetylation is impaired in snf22∆/hrp3∆ cells, suggesting that both redundant ADCRs induce recruitment of Gcn5 to the chromatin array in the fbp1 upstream region. These results reveal a previously unappreciated interplay between ADCRs and histone acetylation in which histone acetylation facilitates recruitment of ADCRs, while ADCRs are required for histone acetylation.

  16. Chromatin structure in the unicellular algae Olisthodiscus luteus, Crypthecodinium cohnii and Peridiniun balticum.

    Science.gov (United States)

    Rizzo, P J; Burghardt, R C

    1980-01-01

    Isolated nuclei of the unicellular alga Olisthodiscus luteus, the uninucleate dinoflagellate Crypthecodinium cohnii and the binucleate dinoflagellate Peridinium balticum were lysed and deposited on grids by the microcentrifugation technique. The ultrastructure of the released chromatin fibers was compared to that of mouse liver nuclei. Chromatin from nuclei of Olisthodiscus luteus and the "eukaryotic" nuclei of Peridinium balticum, appeared as linear arrays of regularly repeating subunits which were identical in size and morphology to mouse nucleosomes. In contrast, the chromatin fibers from Crypthecodinium cohnii nuclei appeared as smoothe threads with a diameter of about 6.5 nm. Nuclear preparations containing mixtures of "dinokaryotic" and "eukaryotic" nuclei of Peridinium balticum also contained smooth fibers which most likely originated from the dinokaryotic nuclei. These and other results demonstrating the presence of nucleosomes in lower eukaryotes suggest that the subunit structure of chromatin arose very early in the evolution of the eukaryotic cell.

  17. Macrogenomic engineering via modulation of the scaling of chromatin packing density.

    Science.gov (United States)

    Almassalha, Luay M; Bauer, Greta M; Wu, Wenli; Cherkezyan, Lusik; Zhang, Di; Kendra, Alexis; Gladstein, Scott; Chandler, John E; VanDerway, David; Seagle, Brandon-Luke L; Ugolkov, Andrey; Billadeau, Daniel D; O'Halloran, Thomas V; Mazar, Andrew P; Roy, Hemant K; Szleifer, Igal; Shahabi, Shohreh; Backman, Vadim

    2017-11-01

    Many human diseases result from the dysregulation of the complex interactions between tens to thousands of genes. However, approaches for the transcriptional modulation of many genes simultaneously in a predictive manner are lacking. Here, through the combination of simulations, systems modelling and in vitro experiments, we provide a physical regulatory framework based on chromatin packing-density heterogeneity for modulating the genomic information space. Because transcriptional interactions are essentially chemical reactions, they depend largely on the local physical nanoenvironment. We show that the regulation of the chromatin nanoenvironment allows for the predictable modulation of global patterns in gene expression. In particular, we show that the rational modulation of chromatin density fluctuations can lead to a decrease in global transcriptional activity and intercellular transcriptional heterogeneity in cancer cells during chemotherapeutic responses to achieve near-complete cancer cell killing in vitro. Our findings represent a 'macrogenomic engineering' approach to modulating the physical structure of chromatin for whole-scale transcriptional modulation.

  18. Chromatin Structure in Bands and Interbands of Polytene Chromosomes Imaged by Atomic Force Microscopy

    NARCIS (Netherlands)

    de Grauw, C.J.; de Grauw, C.J.; Avogadro, A.; van den Heuvel, D.J.; van den Heuvel, D.J.; van der Werf, Kees; Otto, Cornelis; Kraan, Yvonne M.; van Hulst, N.F.; Greve, Jan

    1998-01-01

    Polytene chromosomes from Drosophila melanogaster, observed from squash preparations, and chromosomes from Chironomus thummi thummi, investigated under physiological conditions, are imaged using an Atomic Force Microscope. Various chromatin fiber structures can be observed with high detail in fixed

  19. Molecular composition of the W chromatin in some moth species studied by comparative genomic hybridization (CGH)

    Czech Academy of Sciences Publication Activity Database

    Sahara, K.; Marec, František; Eickhoff, U.; Traut, E.

    09, č. 1 (2001), s. 78 ISSN 0967-3849. [International Chromosome Conference /14./. 04.09.2001-08.09.2001, Wurzburg] Institutional research plan: CEZ:Av0Z5007907 Keywords : W chromatin Subject RIV: EB - Genetics ; Molecular Biology

  20. Applications of high-throughput sequencing to chromatin structure and function in mammals

    OpenAIRE

    Dunham, Ian

    2009-01-01

    High-throughput DNA sequencing approaches have enabled direct interrogation of chromatin samples from mammalian cells. We are beginning to develop a genome-wide description of nuclear function during development, but further data collection, refinement, and integration are needed.

  1. Arabidopsis Chromatin Assembly Factor 1 is required for occupancy and position of a subset of nucleosomes

    Czech Academy of Sciences Publication Activity Database

    Munoz-Viana, R.; Wildhaber, T.; Trejo-Arellano, M.S.; Mozgová, Iva; Hennig, L.

    2017-01-01

    Roč. 92, č. 3 (2017), s. 363-374 ISSN 0960-7412 Institutional support: RVO:61388971 Keywords : Arabidopsis thaliana * chromatin * CAF-1 Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 5.901, year: 2016

  2. Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs

    DEFF Research Database (Denmark)

    Willems, Rhea; Krych, Lukasz; Rybicki, Verena

    2015-01-01

    AIM: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & METHODS: Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure......; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon...... stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03). CONCLUSION: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin...

  3. Micro- and nanoscale devices for the investigation of epigenetics and chromatin dynamics

    Science.gov (United States)

    Aguilar, Carlos A.; Craighead, Harold G.

    2013-10-01

    Deoxyribonucleic acid (DNA) is the blueprint on which life is based and transmitted, but the way in which chromatin -- a dynamic complex of nucleic acids and proteins -- is packaged and behaves in the cellular nucleus has only begun to be investigated. Epigenetic modifications sit 'on top of' the genome and affect how DNA is compacted into chromatin and transcribed into ribonucleic acid (RNA). The packaging and modifications around the genome have been shown to exert significant influence on cellular behaviour and, in turn, human development and disease. However, conventional techniques for studying epigenetic or conformational modifications of chromosomes have inherent limitations and, therefore, new methods based on micro- and nanoscale devices have been sought. Here, we review the development of these devices and explore their use in the study of DNA modifications, chromatin modifications and higher-order chromatin structures.

  4. To spread or not to spread - chromatin modifications in response to DNA damage

    DEFF Research Database (Denmark)

    Altmeyer, M.; Lukas, J.

    2013-01-01

    Chromatin modifications in response to DNA damage are vital for genome integrity. Multiple proteins and pathways required to generate specialized chromatin domains around DNA lesions have been identified and the increasing amount of information calls for unifying concepts that would allow us...... to grasp the ever-increasing complexity. This review aims at contributing to this trend by focusing on feed-forward and feedback mechanisms, which in mammalian cells determine the extent of chromatin modifications after DNA damage. We highlight the emerging notion that the nodal points of these highly...... dynamic pathways operate in a rate-limiting mode, whose deregulation can disrupt physiological boundaries between damaged and undamaged chromatin, dictate repair pathway choice, and determine the fate of cells exposed to genotoxic stress....

  5. Local changes of higher-order chromatin structure during DSB-repair

    International Nuclear Information System (INIS)

    Falk, M; Lukasova, E; Gabrielova, B; Ondrej, V; Kozubek, S

    2008-01-01

    We show that double-strand breaks (DSBs) induced in DNA of human cells by γ-radiation arise mainly in active, gene-rich, decondensed chromatin. We demonstrate that DSBs show limited movement in living cells, occasionally resulting in their permanent clustering, which poses a risk of incorrect DNA rejoining. In addition, some DSBs remain unrepaired for several days after irradiation, forming lesions repairable only with difficulty which are hazardous for genome stability. These 'late' DSBs colocalize with heterochromatin markers (dimethylated histone H3 at lysine 9, HP1 and CENP-A proteins), despite the low density of the surrounding chromatin. This indicates that there is epigenetic silencing of loci close to unrepaired DSBs and/or stabilization of damaged decondensed chromatin loops during repair and post-repair reconstitution of chromatin structure

  6. The ABC Adaptive Fusion Architecture

    DEFF Research Database (Denmark)

    Bunde-Pedersen, Jonathan; Mogensen, Martin; Bardram, Jakob Eyvind

    2006-01-01

    and early implementation of a systemcapable of adapting to its operating environment, choosingthe best fit combination of the client-server and peerto-peer architectures. The architecture creates a seamlessintegration between a centralized hybrid architecture and adecentralized architecture, relying on what...

  7. New Energy Architecture. Myanmar

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    A global transition towards a new energy architecture is under way, driven by countries' need to respond to the changing dynamics of economic growth, environmental sustainability and energy security. The World Economic Forum, in collaboration with Accenture, has created the New Energy Architecture Initiative to address and accelerate this transition. The Initiative supports the development of national strategies and policy frameworks as countries seek to achieve the combined goals of energy security and access, sustainability, and economic growth and development. The World Economic Forum has formed a partnership with the Ministry of Energy of Myanmar to help apply the Initiative's approach to this developing and resource-rich nation. The Asian Development Bank and the World Economic Forum's Project Adviser, Accenture, have collaborated with the Forum on this consultation process, and have been supported by relevant government, industry and civil society stakeholders. The consultation process aims to understand the nation's current energy architecture challenges and provide an overview of a path to a New Energy Architecture through a series of insights. These insights could form the basis for a long-term multistakeholder roadmap to build Myanmar's energy sector in a way that is secure and sustainable, and promotes economic growth as the country makes its democratic transition. While not all recommendations can be implemented in the near term, they do provide options for creating a prioritized roadmap for Myanmar's energy transition. This report is the culmination of a nine-month multistakeholder process investigating Myanmar's energy architecture. Over the course of many visits to the country, the team has conducted numerous interviews, multistakeholder workshops, and learning and data-gathering exercises to ensure a comprehensive range of information and views. The team has also engaged with a variety of stakeholders to better inform their findings, which have come

  8. New Energy Architecture. Myanmar

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2013-06-15

    A global transition towards a new energy architecture is under way, driven by countries' need to respond to the changing dynamics of economic growth, environmental sustainability and energy security. The World Economic Forum, in collaboration with Accenture, has created the New Energy Architecture Initiative to address and accelerate this transition. The Initiative supports the development of national strategies and policy frameworks as countries seek to achieve the combined goals of energy security and access, sustainability, and economic growth and development. The World Economic Forum has formed a partnership with the Ministry of Energy of Myanmar to help apply the Initiative's approach to this developing and resource-rich nation. The Asian Development Bank and the World Economic Forum's Project Adviser, Accenture, have collaborated with the Forum on this consultation process, and have been supported by relevant government, industry and civil society stakeholders. The consultation process aims to understand the nation's current energy architecture challenges and provide an overview of a path to a New Energy Architecture through a series of insights. These insights could form the basis for a long-term multistakeholder roadmap to build Myanmar's energy sector in a way that is secure and sustainable, and promotes economic growth as the country makes its democratic transition. While not all recommendations can be implemented in the near term, they do provide options for creating a prioritized roadmap for Myanmar's energy transition. This report is the culmination of a nine-month multistakeholder process investigating Myanmar's energy architecture. Over the course of many visits to the country, the team has conducted numerous interviews, multistakeholder workshops, and learning and data-gathering exercises to ensure a comprehensive range of information and views. The team has also engaged with a variety of stakeholders to better

  9. Effect of Seminal Vesicles and Dithiotritol (Dtt on Stability of Sperm Chromatin

    Directory of Open Access Journals (Sweden)

    MH Nasr-Esfahani

    2005-04-01

    Full Text Available Introduction: Different studies have shown that there is no relation between sperm chromatin stability and fertilization rate in both IVF and ICSI patients. However, the relation between SDS tests, as a detergent, along with DTT as reducer of disulphide bridges has not been studied so far in ICSI patients. Since different concentrations of DTT can induce different degrees of sperm chromatin decondensation, the aim of this study was to evaluate the effect of different concentrations of DTT on sperm chromatin decondensation in IVF and ICSI cases. Methods: During this study, 85 patients were divided into two groups according to their treatment procedure (IVF or ICSI.Semen samples of each patient was evaluated for sperm chromatin tests including SDS, SDS+EDTA & SDS+DTT for assessment of free thiole groups level (-SH, amount of non covalent bond between Zn and thioles(-SH Zn SH- and levels of disulfide bond (-S-S- in sperm chromatin, respectively. In this study, seminal fructose concentration, corrected seminal fructose level and true corrected fructose level as indicators of seminal vesicle function on sperm chromatin stability were assessed. Results: No correlation was observed between any of the above tests and rate of fertilization, both in IVF and ICSI cases. However, in IVF patients, a significant correlation was observed between SDS, SDS+DTT test and seminal fructose level, while in ICSI patients, only a significant correlation was observed between SDS+DTT and corrected or true fructose concentration. Conclusion: Since no correlation was observed between sperm chromatin test and fertilization rate, it is suggested that the chromatin status of these samples are adequate for fertilization to take place and extent of disulphide bridges has no effect on fertilization rate. However, the amount of disulphide bound present in sperms of ICSI and IVF patients are different, and this difference is related to seminal vesicle performance in these patients.

  10. Specific distribution of the Saccharomyces cerevisiae linker histone homolog HHO1p in the chromatin

    OpenAIRE

    Freidkin, Ilya; Katcoff, Don J.

    2001-01-01

    In virtually all eukaryotic organisms, linker DNA between nucleosomes is associated with a histone termed linker histone or histone H1. In Saccharomyces cerevisiae, HHO1 encodes a putative linker histone with very significant homology to histone H1. The encoded protein is expressed in the nucleus, but has not been shown to affect global chromatin structure, nor has its deletion shown any detectable phenotype. In vitro chromatin assembly experiments with recombinant HHO1p have shown that it is...

  11. eRNAs promote transcription by establishing chromatin accessibility at defined genomic loci

    DEFF Research Database (Denmark)

    Mousavi, Kambiz; Zare, Hossein; Dell'orso, Stefania

    2013-01-01

    )RNA acted to activate the downstream myogenic genes. The deployment of transcriptional machinery to appropriate loci is contingent on chromatin accessibility, a rate-limiting step preceding Pol II assembly. By nuclease sensitivity assay, we found that eRNAs regulate genomic access of the transcriptional...... complex to defined regulatory regions. In conclusion, our data suggest that eRNAs contribute to establishing a cell-type-specific transcriptional circuitry by directing chromatin-remodeling events....

  12. ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome.

    Directory of Open Access Journals (Sweden)

    Gary Hon

    2008-10-01

    Full Text Available Computational methods to identify functional genomic elements using genetic information have been very successful in determining gene structure and in identifying a handful of cis-regulatory elements. But the vast majority of regulatory elements have yet to be discovered, and it has become increasingly apparent that their discovery will not come from using genetic information alone. Recently, high-throughput technologies have enabled the creation of information-rich epigenetic maps, most notably for histone modifications. However, tools that search for functional elements using this epigenetic information have been lacking. Here, we describe an unsupervised learning method called ChromaSig to find, in an unbiased fashion, commonly occurring chromatin signatures in both tiling microarray and sequencing data. Applying this algorithm to nine chromatin marks across a 1% sampling of the human genome in HeLa cells, we recover eight clusters of distinct chromatin signatures, five of which correspond to known patterns associated with transcriptional promoters and enhancers. Interestingly, we observe that the distinct chromatin signatures found at enhancers mark distinct functional classes of enhancers in terms of transcription factor and coactivator binding. In addition, we identify three clusters of novel chromatin signatures that contain evolutionarily conserved sequences and potential cis-regulatory elements. Applying ChromaSig to a panel of 21 chromatin marks mapped genomewide by ChIP-Seq reveals 16 classes of genomic elements marked by distinct chromatin signatures. Interestingly, four classes containing enrichment for repressive histone modifications appear to be locally heterochromatic sites and are enriched in quickly evolving regions of the genome. The utility of this approach in uncovering novel, functionally significant genomic elements will aid future efforts of genome annotation via chromatin modifications.

  13. A high-resolution map of the three-dimensional chromatin interactome in human cells.

    Science.gov (United States)

    Jin, Fulai; Li, Yan; Dixon, Jesse R; Selvaraj, Siddarth; Ye, Zhen; Lee, Ah Young; Yen, Chia-An; Schmitt, Anthony D; Espinoza, Celso A; Ren, Bing

    2013-11-14

    A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lack either the resolution or coverage to permit a whole-genome, unbiased view of chromatin interactions. Here we report a comprehensive chromatin interaction map generated in human fibroblasts using a genome-wide 3C analysis method (Hi-C). We determined over one million long-range chromatin interactions at 5-10-kb resolution, and uncovered general principles of chromatin organization at different types of genomic features. We also characterized the dynamics of promoter-enhancer contacts after TNF-α signalling in these cells. Unexpectedly, we found that TNF-α-responsive enhancers are already in contact with their target promoters before signalling. Such pre-existing chromatin looping, which also exists in other cell types with different extracellular signalling, is a strong predictor of gene induction. Our observations suggest that the three-dimensional chromatin landscape, once established in a particular cell type, is relatively stable and could influence the selection or activation of target genes by a ubiquitous transcription activator in a cell-specific manner.

  14. Chk1 protects against chromatin bridges by constitutively phosphorylating BLM serine 502 to inhibit BLM degradation.

    Science.gov (United States)

    Petsalaki, Eleni; Dandoulaki, Maria; Morrice, Nick; Zachos, George

    2014-09-15

    Chromatin bridges represent incompletely segregated chromosomal DNA connecting the anaphase poles and can result in chromosome breakage. The Bloom's syndrome protein helicase (BLM, also known as BLMH) suppresses formation of chromatin bridges. Here, we show that cells deficient in checkpoint kinase 1 (Chk1, also known as CHEK1) exhibit higher frequency of chromatin bridges and reduced BLM protein levels compared to controls. Chk1 inhibition leads to BLM ubiquitylation and proteasomal degradation during interphase. Furthermore, Chk1 constitutively phosphorylates human BLM at serine 502 (S502) and phosphorylated BLM localises to chromatin bridges. Mutation of S502 to a non-phosphorylatable alanine residue (BLM-S502A) reduces the stability of BLM, whereas expression of a phospho-mimicking BLM-S502D, in which S502 is mutated to aspartic acid, stabilises BLM and prevents chromatin bridges in Chk1-deficient cells. In addition, wild-type but not BLM-S502D associates with cullin 3, and cullin 3 depletion rescues BLM accumulation and localisation to chromatin bridges after Chk1 inhibition. We propose that Chk1 phosphorylates BLM-S502 to inhibit cullin-3-mediated BLM degradation during interphase. These results suggest that Chk1 prevents deleterious anaphase bridges by stabilising BLM. © 2014. Published by The Company of Biologists Ltd.

  15. A Poly-ADP-Ribose Trigger Releases the Auto-Inhibition of a Chromatin Remodeling Oncogene.

    Science.gov (United States)

    Singh, Hari R; Nardozza, Aurelio P; Möller, Ingvar R; Knobloch, Gunnar; Kistemaker, Hans A V; Hassler, Markus; Harrer, Nadine; Blessing, Charlotte; Eustermann, Sebastian; Kotthoff, Christiane; Huet, Sébastien; Mueller-Planitz, Felix; Filippov, Dmitri V; Timinszky, Gyula; Rand, Kasper D; Ladurner, Andreas G

    2017-12-07

    DNA damage triggers chromatin remodeling by mechanisms that are poorly understood. The oncogene and chromatin remodeler ALC1/CHD1L massively decompacts chromatin in vivo yet is inactive prior to DNA-damage-mediated PARP1 induction. We show that the interaction of the ALC1 macrodomain with the ATPase module mediates auto-inhibition. PARP1 activation suppresses this inhibitory interaction. Crucially, release from auto-inhibition requires a poly-ADP-ribose (PAR) binding macrodomain. We identify tri-ADP-ribose as a potent PAR-mimic and synthetic allosteric effector that abrogates ATPase-macrodomain interactions, promotes an ungated conformation, and activates the remodeler's ATPase. ALC1 fragments lacking the regulatory macrodomain relax chromatin in vivo without requiring PARP1 activation. Further, the ATPase restricts the macrodomain's interaction with PARP1 under non-DNA damage conditions. Somatic cancer mutants disrupt ALC1's auto-inhibition and activate chromatin remodeling. Our data show that the NAD + -metabolite and nucleic acid PAR triggers ALC1 to drive chromatin relaxation. Modular allostery in this oncogene tightly controls its robust, DNA-damage-dependent activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Formation of DNA-protein crosslinks in gamma-irradiated chromatin

    International Nuclear Information System (INIS)

    Mee, L.K.

    1985-01-01

    Gamma-irradiation of chromatin in vitro and in vivo induces DNA-protein crosslinks which are stable to salt and detergent treatment. The efficiency of crosslink formation is 100 times greater in irradiated isolated chromatin than in chromatin irradiated in cells before isolation. Gamma-irradiation of isolated chromatin in the presence of radical scavengers shows that OH . is the most effective radical for the promotion of crosslinking whereas e/sub aq//sup -/ and O/sub 2//sup -/ are essentially ineffective. For chromatin irradiated in the cell before isolation, fewer crosslinks are formed in air than in an atmosphere of nitrogen; the greatest effect is found in cells irradiated in an atmosphere of nitrous oxide, suggesting that OH . may be involved in the formation of crosslinks in vivo. On the basis of comparing radiation-induced crosslinking in whole chromating (DNA, H1 histone, the core histones - H2A, H2B, H3 and H4 - and non-histone chromosomal proteins) and in a chromatin subunit (DNA and the core histones), the authors identified the core histones as the specific chromosomal proteins predominantly involved in crosslinking to DNA

  17. Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandre A.S.F. Raposo

    2015-03-01

    Full Text Available The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.

  18. Towards a semantic web layered architecture

    CSIR Research Space (South Africa)

    Gerber, AJ

    2007-02-01

    Full Text Available as an architectural pattern or architectural style [6, 43]. In this section we give a brief description of the con- cepts software architecture and layered architecture. In ad- dition we provide a summary of a list of criteria for layered architectures identified...- els caused some architectural recurrences to evolve. These are described as architectural patterns [6] or architectural styles [43]. Examples of the best known architectural patterns include, but are not limited to, the client/server architectural...

  19. Neural Architectures for Control

    Science.gov (United States)

    Peterson, James K.

    1991-01-01

    The cerebellar model articulated controller (CMAC) neural architectures are shown to be viable for the purposes of real-time learning and control. Software tools for the exploration of CMAC performance are developed for three hardware platforms, the MacIntosh, the IBM PC, and the SUN workstation. All algorithm development was done using the C programming language. These software tools were then used to implement an adaptive critic neuro-control design that learns in real-time how to back up a trailer truck. The truck backer-upper experiment is a standard performance measure in the neural network literature, but previously the training of the controllers was done off-line. With the CMAC neural architectures, it was possible to train the neuro-controllers on-line in real-time on a MS-DOS PC 386. CMAC neural architectures are also used in conjunction with a hierarchical planning approach to find collision-free paths over 2-D analog valued obstacle fields. The method constructs a coarse resolution version of the original problem and then finds the corresponding coarse optimal path using multipass dynamic programming. CMAC artificial neural architectures are used to estimate the analog transition costs that dynamic programming requires. The CMAC architectures are trained in real-time for each obstacle field presented. The coarse optimal path is then used as a baseline for the construction of a fine scale optimal path through the original obstacle array. These results are a very good indication of the potential power of the neural architectures in control design. In order to reach as wide an audience as possible, we have run a seminar on neuro-control that has met once per week since 20 May 1991. This seminar has thoroughly discussed the CMAC architecture, relevant portions of classical control, back propagation through time, and adaptive critic designs.

  20. The Effects of Betaine on the Nuclear Fractal Dimension, Chromatin Texture, and Proliferative Activity in Hepatocytes in Mouse Model of Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Vesković, Milena; Labudović-Borović, Milica; Zaletel, Ivan; Rakočević, Jelena; Mladenović, Dušan; Jorgačević, Bojan; Vučević, Danijela; Radosavljević, Tatjana

    2018-04-01

    The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters. MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity were less prominent in the MCD+BET group compared with the MCD group. Angular second moment (ASM) and inverse difference moment (IDM) (textural homogeneity markers) were significantly increased in the MCD+BET group versus the MCD group (pMCD and the control group was evident. Heterogeneity parameters, contrast, and correlation were significantly increased in the MCD group versus the control (pMCD group (pMCD diet-induced NAFLD by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine supplementation increased nuclear homogeneity and chromatin complexity with reduction of entropy, contrast, and correlation.

  1. Extracellular Matrix, Nuclear and Chromatin Structure and GeneExpression in Normal Tissues and Malignant Tumors: A Work inProgress

    Energy Technology Data Exchange (ETDEWEB)

    Spencer, Virginia A.; Xu, Ren; Bissell, Mina J.

    2006-08-01

    Almost three decades ago, we presented a model where theextracellular matrix (ECM) was postulated to influence gene expressionand tissue-specificity through the action of ECM receptors and thecytoskeleton. This hypothesis implied that ECM molecules could signal tothe nucleus and that the unit of function in higher organisms was not thecell alone, but the cell plus its microenvironment. We now know that ECMinvokes changes in tissue and organ architecture and that tissue, cell,nuclear, and chromatin structure are changed profoundly as a result ofand during malignant progression. Whereas some evidence has beengenerated for a link between ECM-induced alterations in tissuearchitecture and changes in both nuclear and chromatin organization, themanner by which these changes actively induce or repress gene expressionin normal and malignant cells is a topic in need of further attention.Here, we will discuss some key findings that may provide insights intomechanisms through which ECM could influence gene transcription and howtumor cells acquire the ability to overcome these levels ofcontrol.

  2. Architecture is Life... ...Life is Architecture

    OpenAIRE

    Snider, David E

    2001-01-01

    When thinking about architecture, I cannot help but think about my life and the things that have affected my life. How does the environment around us effect the daily decisions we make? How do the experiences throughout our life impact who we are and who we become? The people and surroundings we choose will ultimately decide the type of people we become. When we select our surroundings we are in turn selecting our ideal community. Everyone is trying to achieve community in some sense, from in...

  3. Base Camp Architecture

    Directory of Open Access Journals (Sweden)

    Warebi Gabriel Brisibe

    2016-03-01

    Full Text Available Longitudinal or time line studies of change in the architecture of a particular culture are common, but an area still open to further research is change across space or place. In particular, there is need for studies on architectural change of cultures stemming from the same ethnic source split between their homeland and other Diasporas. This change may range from minor deviations to drastic shifts away from an architectural norm and the accumulation of these shifts within a time frame constitutes variations. This article focuses on identifying variations in the architecture of the Ijo fishing group that migrates along the coastline of West Africa. It examines the causes of cross-cultural variation between base camp dwellings of Ijo migrant fishermen in the Bakassi Peninsula in Cameroon and Bayelsa State in Nigeria. The study draws on the idea of the inevitability of cultural and social change over time as proposed in the theories of cultural dynamism and evolution. It tests aspects of cultural transmission theory using the principal coordinates analysis to ascertain the possible causes of variation. From the findings, this research argues that migration has enhanced the forces of cultural dynamism, which have resulted in significant variations in the architecture of this fishing group.

  4. Architecture and Phenomenology: Introduction

    Directory of Open Access Journals (Sweden)

    Brendan O’ Byrne

    2014-07-01

    Full Text Available The implications of philosophical aesthetics in the consideration of architecture have been relatively slight. Part of the reason is the neglect of architecture in the work of Baumgarten, Burke and Kant. Within the discourse of architecture the questions raised for philosophical consideration arising out of practice restricted the area of reflection and investigation. The dominant positions were to become either a version of neo-Kantianism, or a direct re-working of Hegel’s Lectures on Aesthetics. The significance of Kant’s distinction between ‘free’ and ‘dependent beauty’ is analysed, and in consequence the need to philosophically question again the relation of architecture to buiding, to dwelling and space. For this the question of accessibility as raised in the phenomenological enquiry, in the work of Brentano, Sartre, Bachelard, Merleau-Ponty, and especially Heidegger points to a different route for the appraisal of philosophical and architectural relations which are exhibited in the contributions of the 10 authors to this issue of Footprint.

  5. Architecture and Phenomenology: Introduction

    Directory of Open Access Journals (Sweden)

    Brendan O’ Byrne

    2008-10-01

    Full Text Available The implications of philosophical aesthetics in the consideration of architecture have been relatively slight. Part of the reason is the neglect of architecture in the work of Baumgarten, Burke and Kant. Within the discourse of architecture the questions raised for philosophical consideration arising out of practice restricted the area of reflection and investigation. The dominant positions were to become either a version of neo-Kantianism, or a direct re-working of Hegel’s Lectures on Aesthetics. The significance of Kant’s distinction between ‘free’ and ‘dependent beauty’ is analysed, and in consequence the need to philosophically question again the relation of architecture to building, to dwelling and space. For this the question of accessibility as raised in the phenomenological enquiry, in the work of Brentano, Sartre, Bachelard, Merleau-Ponty, and especially Heidegger points to a different route for the appraisal of philosophical and architectural relations which are exhibited in the contributions of the 10 authors to this issue of Footprint.

  6. The Simulation Intranet Architecture

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, V.P.; Linebarger, J.M.; Miller, D.J.; Vandewart, R.L.

    1998-12-02

    The Simdarion Infranet (S1) is a term which is being used to dcscribc one element of a multidisciplinary distributed and distance computing initiative known as DisCom2 at Sandia National Laboratory (http ct al. 1998). The Simulation Intranet is an architecture for satisfying Sandia's long term goal of providing an end- to-end set of scrviccs for high fidelity full physics simu- lations in a high performance, distributed, and distance computing environment. The Intranet Architecture group was formed to apply current distributed object technologies to this problcm. For the hardware architec- tures and software models involved with the current simulation process, a CORBA-based architecture is best suited to meet Sandia's needs. This paper presents the initial desi-a and implementation of this Intranct based on a three-tier Network Computing Architecture(NCA). The major parts of the architecture include: the Web Cli- ent, the Business Objects, and Data Persistence.

  7. Globalization and Landscape Architecture

    Directory of Open Access Journals (Sweden)

    Robert R. Hewitt

    2014-02-01

    Full Text Available The literature review examines globalization and landscape architecture as discourse, samples its various meanings, and proposes methods to identify and contextualize its specific literature. Methodologically, the review surveys published articles and books by leading authors and within the WorldCat.org Database associated with landscape architecture and globalization, analyzing survey results for comprehensive conceptual and co-relational frameworks. Three “higher order” dimensions frame the review’s conceptual organization, facilitating the organization of subordinate/subtopical areas of interest useful for comparative analysis. Comparative analysis of the literature suggests an uneven clustering of discipline-related subject matter across the literature’s “higher order” dimensions, with a much smaller body of literature related to landscape architecture confined primarily to topics associated with the dispersion of global phenomena. A subcomponent of this smaller body of literature is associated with other fields of study, but inferentially related to landscape architecture. The review offers separate references and bibliographies for globalization literature in general and globalization and landscape architecture literature, specifically.

  8. The possible role of chromatin conformation changes in adaptive responses to ionizing radiation

    International Nuclear Information System (INIS)

    Ekhtiar, A.; Ammer, A.; Jbawi, A.; Othman, A.

    2012-05-01

    Organisms are affected by different DNA damaging agents naturally present in the environment or released as a result of human activity. Many defense mechanisms have evolved in organisms to minimize genotoxic damage. One of them is induced radioresistance or adaptive response. The adaptive response could be considered as a nonspecific phenomenon in which exposure to minimal stress could result in increased resistance to higher levels of the same or to other types of stress some hours later. A better understanding of the molecular mechanism underlying the adaptive response may lead to an improvement of cancer treatment, risk assessment and risk management strategies, radiation protection. The aim of current study was to study the possible role of chromatin conformation changes induced by ionizing radiation on the adaptive responses in human lymphocyte. For this aim the chromatin conformation have been studied in human lymphocytes from three non-smoking and three smoking healthy volunteers prior, and after espouser to gamma radiation (adaptive dose 0.1 Gy, challenge dose 1.5 Gy and adaptive + dose challenge). Chromosomal aberrations and micronucleus have been used as end point to study radio cytotoxicity and adaptive response. Our results indicated individual differences in radio adaptive response and the level of this response was dependent of chromatin de condensation induced by a adaptive small dose.The results showed that different dose of gamma rays induce a chromatin de condensation in human lymphocyte. The maximum chromatin relaxation were record when lymphocyte exposed to adaptive dose (0.1 Gy.). Results also showed that Adaptive dose have affected on the induction of challenge dose (1.5 Gy) of chromosome aberration and micronucleus . The comparison of results of chromatin de condensation induction as measured by flow cytometry and cytogenetic damages measured by chromosomal aberrations or micronucleus, was showed a proportionality of adaptive response with

  9. APPLICATION OF THE SPERM CHROMATIN STRUCTURE ASSAY TO THE TEPLICE PROGRAM SEMEN STUDIES: A NEW METHOD FOR EVALUATING SPERM NUCLEAR CHROMATIN DAMAGE

    Science.gov (United States)

    ABSTRACTA measure of sperm chromatin integrity was added to the routine semen end points evaluated in the Teplice Program male reproductive health studies. To address the hypothesis that exposure to periods of elevated air pollution may be associated with abnormalities in sp...

  10. Circulating chromatin-anti-chromatin antibody complexes bind with high affinity to dermo-epidermal structures in murine and human lupus nephritis

    DEFF Research Database (Denmark)

    Fismen, S; Hedberg, A; Fenton, K A

    2009-01-01

    Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo-epidermal i......Murine and human lupus nephritis are characterized by glomerular deposits of electron-dense structures (EDS). Dominant components of EDS are chromatin fragments and IgG antibodies. Whether glomerular EDS predispose for similar deposits in skin is unknown. We analysed (i) whether dermo......-epidermal immune complex deposits have similar molecular composition as glomerular deposits, (ii) whether chromatin fragments bind dermo-epidermal structures, and (iii) whether deposits in nephritic glomeruli predispose for accumulation of similar deposits in skin. Paired skin and kidney biopsies from nephritic...... (NZBxNZW)F1 and MRL-lpr/lpr mice and from five patients with lupus nephritis were analysed by immunofluorescence, immune electron microscopy (IEM) and co-localization TUNEL IEM. Affinity of chromatin fragments for membrane structures was determined by surface plasmon resonance. Results demonstrated (i...

  11. rDNA genetic imbalance and nucleolar chromatin restructuring is induced by distant hybridization between Raphanus sativus and Brassica alboglabra.

    Directory of Open Access Journals (Sweden)

    Hong Long

    Full Text Available The expression of rDNA in hybrids inherited from only one progenitor refers to nucleolar dominance. The molecular basis for choosing which genes to silence remains unclear. We report genetic imbalance induced by distant hybridization correlates with formation of rDNA genes (NORs in the hybrids between Raphanus sativus L. and Brassica alboglabra Bailey. Moreover, increased CCGG methylation of rDNA in F1 hybrids is concomitant with Raphanus-derived rDNA gene silencing and rDNA transcriptional inactivity revealed by nucleolar configuration restriction. Newly formed rDNA gene locus occurred through chromosomal in F1 hybrids via chromosomal imbalance. NORs are gained de novo, lost, and/or transposed in the new genome. Inhibition of methyltransferases leads to changes in nucleolar architecture, implicating a key role of methylation in control of nucleolar dominance and vital nucleolar configuration transition. Our findings suggest that gene imbalance and methylation-related chromatin restructuring is important for rDNA gene silencing that may be crucial for synthesis of specific proteins.

  12. Trans-architecture

    Directory of Open Access Journals (Sweden)

    Tim Gough

    2017-12-01

    Full Text Available Starting from the intense experience of the gay club, this paper asks whether that experience or event can be acknowledged by architectural theory. Via a reading of Judith Butler’s Gender Trouble and Jacques Derrida’s Before the Law, it posits that the transing of gender can be a clue as to the transing of architecture away from essentialising ontologies. It then uses Deleuze and Guattari’s idea of an assemblage to show how this can be done, making reference to the assemblage of the gay seduction scene in Proust’s Remembrance of Things Past and the image of the interplay of orchid and wasp that is inspired by it. The paper concludes by showing how this ontology relates to a specific instance of transing architecture in the gay and SM clubs of Vauxhall, South London.

  13. Agent Architectures for Compliance

    Science.gov (United States)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  14. Towards an Architectural Anthropology

    DEFF Research Database (Denmark)

    Stender, Marie

    2017-01-01

    Architecture and anthropology have always had overlapping interests regarding issues such as spatial organisation, forms of human dwellings, and the interplay between social life and physical surroundings. Recent developments in both disciplines make it even more relevant to explore and evolve...... their overlaps and collaboration. However, there are also challenging differences to take into account regarding disciplinary traditions of, for example, communication, temporality, and normativity. This article explores the potentials and challenges of architectural anthropology as a distinct sub......-discipline and outlines its possible theoretical, methodological, and applied contributions. It is proposed that the ambition to understand people in a different way than they understand themselves is key in both disciplines, and that architectural anthropology is consequently not only relevant in studies of vernacular...

  15. Islamic Architecture and Arch

    Directory of Open Access Journals (Sweden)

    Mohammed Mahbubur Rahman

    2015-01-01

    Full Text Available The arch, an essential architectural element since the early civilizations, permitted the construction of lighter walls and vaults, often covering a large span. Visually it was an important decorative feature that was trans-mitted from architectural decoration to other forms of art worldwide. In early Islamic period, Muslims were receiving from many civilizations, which they improved and re-introduced to bring about the Renaissance. Arches appeared in Mesopotamia, Indus, Egyptian, Babylonian, Greek and Assyrian civilizations; but the Romans applied the technique to a wide range of structures. The Muslims mastered the use and design of the arch, employed for structural and functional purposes, progressively meeting decorative and symbolic pur-poses. Islamic architecture is characterized by arches employed in all types of buildings; most common uses being in arcades. This paper discusses the process of assimilation and charts how they contributed to other civilizations.

  16. Architecture of Environmental Engineering

    DEFF Research Database (Denmark)

    Wenzel, Henrik; Alting, Leo

    2006-01-01

    An architecture of Environmental Engineering has been developed comprising the various disciplines and tools involved. It identifies industry as the major actor and target group, and it builds on the concept of Eco-efficiency. To improve Eco-efficiency, there is a limited number of intervention......-efficiency is the aim of Environmental Engineering, the discipline of synthesis – design and creation of solutions – will form a core pillar of the architecture. Other disciplines of Environmental Engineering exist forming the necessary background and frame for the synthesis. Environmental Engineering, thus, in essence...... comprise the disciplines of: management, system description & inventory, analysis & assessment, prioritisation, synthesis, and communication, each existing at all levels of intervention. The developed architecture of Environmental Engineering, thus, consists of thirty individual disciplines, within each...

  17. Architectural Competition and BIM

    DEFF Research Database (Denmark)

    Sørensen, Nils Lykke; Frandsen, Anne Kathrine; Øien, Turid Borgestrand

    2015-01-01

    on architecturalcompetitions, a series of interviews was conducted with building clients as well as architects, focusing on the impact of the above-mentioned changes within the building sector on architectural competitions as an institution. In the interviews, ICT and notleast BIM was a recurring theme that both parties saw...... as having a positive impact on competitions. But when looking closely into the answers, these revealed diverse understandings of how and why the impact of BIM on competitions could be said to be positive. The paper sheds light on the interaction between the actors (building clients, architects and client...... consultants) and the applied technologies (competition forms, ICT tools, directives) in architectural competitions in a theoretical actor-network perspective. The diverging understandings of the role of BIM are demonstrating one of many negotiations in progress in the network of architectural competitions...

  18. Persian architecture and mathematics

    CERN Document Server

    2012-01-01

    This volulme features eight original papers dedicated to the theme “Persian Architecture and Mathematics,” guest edited by Reza Sarhangi. All papers were approved through a rigorous process of blind peer review and edited by an interdisciplinary scientific editorial committee. Topics range from symmetry in ancient Persian architecture to the elaborate geometric patterns and complex three-dimensional structures of standing monuments of historical periods, from the expression of mathematical ideas to architectonic structures, and from decorative ornament to the representation of modern group theory and quasi-crystalline patterns. The articles discuss unique monuments Persia, including domed structures and two-dimensional patterns, which have received significant scholarly attention in recent years. This book is a unique contribution to studies of Persian architecture in relation to mathematics.

  19. Art and Architectural Space

    DEFF Research Database (Denmark)

    Unterrainer, Walter

    2014-01-01

    the number of museums went up from 300 by 1980 to estimated 3000 museums by 2015. In urban discourses, new museums and buildings for art have been considered as drivers for ´cultural sustainability´ of cities. The notion is diffuse and the reality is more an economic centred ´city branding´ to help...... the promotion of tourism. What surprises: in many cities, the buildings for art are better known and more published and discussed than the art they accommodate. A lot of them are considered as art objects. This raises two questions: How much is architecture itself a form of arts? (in Western architecture...... historically considered even the mother of all arts) - but more relevant: what are appropriate architectural spaces for presenting, exhibiting, contemplating, reflecting, meditating, discussing, enjoying, dissenting, debating creations of art. Simplified, this is a question about the relation between package...

  20. Performative Urban Architecture

    DEFF Research Database (Denmark)

    Thomsen, Bo Stjerne; Jensen, Ole B.

    The paper explores how performative urban architecture can enhance community-making and public domain using socio-technical systems and digital technologies to constitute an urban reality. Digital medias developed for the web are now increasingly occupying the urban realm as a tool for navigating...... the physical world e.g. as exemplified by the Google Walk Score and the mobile extension of the Google Maps to the iPhone. At the same time the development in pervasive technologies and situated computing extends the build environment with digital feedback systems that are increasingly embedded and deployed...... using sensor technologies opening up for new access considerations in architecture as well as the ability for a local environment to act as real-time sources of information and facilities. Starting from the NoRA pavilion for the 10th International Architecture Biennale in Venice the paper discusses...