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.
Willenbrock, Hanni; Ussery, David
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....
Ingstrup, Mads; Hansen, Klaus Marius
Recent research shows runtime architectural reflection is instrumental in, for instance, building adaptive and flexible systems or checking correspondence between design and implementation. Moreover, experience with computational reflection in various branches of computer science shows that the...... interface through which the meta-information of the running system is accessed, and possibly modified, lies at the heart of designing reflective systems. This paper proposes that such an interface should be like a database: accessed through queries expressed using the concepts with which architecture is...... described. Specifically, our contributions are: (1) a presentation of the general idea of a query-based approach to architectural reflection, (2) a definition of an Architectural Query Language (AQL) in which perspectives on an architectural model can be expressed as queries, (3) a prototype of a system...
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.
HUANG Gang; MEI Hong; YANG Fuqing
There exists a consensus that software architecture (SA) plays a central role in software development and also plays an important role in the lifecycle phases after software delivery. Particularly, SA can be used to reduce the great difficulty and cost of software maintenance and evolution. In this paper, runtime software architecture (RSA) based on reflective middleware is proposed to support architecture-based software maintenance and evolution. In this approach, the actual states and behaviors of the runtime system can be observed and manipulated in a consistent and understandable way through its architectural view. Being an accurate, up-to-date, semantic and operable view of SA, RSA looks components and connectors as "white-box" entities to accurately and thoroughly describe the runtime system, extends traditional architecture description languages to formally describe itself and naturally inherit plentiful semantics in traditional views of SA, and utilizes reflective middleware to observe and manipulate the runtime system. In order to demonstrate the feasibility of this approach, a reflective J2EE application server, called PKUAS, is implemented to observe and manipulate the components, connectors and constraints in the runtime system. Finally, the performance evaluation proves that making RSA explicit and operable at runtime has little effect on the runtime system.
Ma, Zhibo; Li, Mo; Roy, Sharmila; Liu, Kevin J; Romine, Matthew L; Lane, Derrick C; Patel, Sapna K; Cai, Haini N
The three-dimensional (3D) organization of the eukaryotic genome is critical for its proper function. Evidence suggests that extensive chromatin loops form the building blocks of the genomic architecture, separating genes and gene clusters into distinct functional domains. These loops are anchored in part by a special type of DNA elements called chromatin boundary elements (CBEs). CBEs were originally found to insulate neighboring genes by blocking influences of transcriptional enhancers or the spread of silent chromatin. However, recent results show that chromatin loops can also play a positive role in gene regulation by looping out intervening DNA and "delivering" remote enhancers to gene promoters. In addition, studies from human and model organisms indicate that the configuration of chromatin loops, many of which are tethered by CBEs, is dynamically regulated during cell differentiation. In particular, a recent work by Li et al has shown that the SF1 boundary, located in the Drosophila Hox cluster, regulates local genes by tethering different subsets of chromatin loops: One subset enclose a neighboring gene ftz, limiting its access by the surrounding Scr enhancers and restrict the spread of repressive histones during early embryogenesis; and the other loops subdivide the Scr regulatory region into independent domains of enhancer accessibility. The enhancer-blocking activity of these CBE elements varies greatly in strength and tissue distribution. Further, tandem pairing of SF1 and SF2 facilitate the bypass of distal enhancers in transgenic flies, providing a mechanism for endogenous enhancers to circumvent genomic interruptions resulting from chromosomal rearrangement. This study demonstrates how a network of chromatin boundaries, centrally organized by SF1, can remodel the 3D genome to facilitate gene regulation during development. PMID:27621770
Ma, Zhibo; Li, Mo; Roy, Sharmila; Liu, Kevin J; Romine, Matthew L; Lane, Derrick C; Patel, Sapna K; Cai, Haini N
The three-dimensional (3D) organization of the eukaryotic genome is critical for its proper function. Evidence suggests that extensive chromatin loops form the building blocks of the genomic architecture, separating genes and gene clusters into distinct functional domains. These loops are anchored in part by a special type of DNA elements called chromatin boundary elements (CBEs). CBEs were originally found to insulate neighboring genes by blocking influences of transcriptional enhancers or the spread of silent chromatin. However, recent results show that chromatin loops can also play a positive role in gene regulation by looping out intervening DNA and “delivering” remote enhancers to gene promoters. In addition, studies from human and model organisms indicate that the configuration of chromatin loops, many of which are tethered by CBEs, is dynamically regulated during cell differentiation. In particular, a recent work by Li et al has shown that the SF1 boundary, located in the Drosophila Hox cluster, regulates local genes by tethering different subsets of chromatin loops: One subset enclose a neighboring gene ftz, limiting its access by the surrounding Scr enhancers and restrict the spread of repressive histones during early embryogenesis; and the other loops subdivide the Scr regulatory region into independent domains of enhancer accessibility. The enhancer-blocking activity of these CBE elements varies greatly in strength and tissue distribution. Further, tandem pairing of SF1 and SF2 facilitate the bypass of distal enhancers in transgenic flies, providing a mechanism for endogenous enhancers to circumvent genomic interruptions resulting from chromosomal rearrangement. This study demonstrates how a network of chromatin boundaries, centrally organized by SF1, can remodel the 3D genome to facilitate gene regulation during development.
Van Bortle, Kevin; Corces, Victor G.
Eukaryotic genomes are intricately arranged into highly organized yet dynamic structures that underlie patterns of gene expression and cellular identity. The recent adaptation of novel genomic strategies for assaying nuclear architecture has significantly extended and accelerated our ability to query the nature of genome organization and the players involved. In particular, recent explorations of physical arrangements and chromatin landscapes in higher eukaryotes have demonstrated that chroma...
Schep, Alicia N; Buenrostro, Jason D; Denny, Sarah K; Schwartz, Katja; Sherlock, Gavin; Greenleaf, William J
Transcription factors canonically bind nucleosome-free DNA, making the positioning of nucleosomes within regulatory regions crucial to the regulation of gene expression. Using the assay of transposase accessible chromatin (ATAC-seq), we observe a highly structured pattern of DNA fragment lengths and positions around nucleosomes in Saccharomyces cerevisiae, and use this distinctive two-dimensional nucleosomal "fingerprint" as the basis for a new nucleosome-positioning algorithm called NucleoATAC. We show that NucleoATAC can identify the rotational and translational positions of nucleosomes with up to base-pair resolution and provide quantitative measures of nucleosome occupancy in S. cerevisiae, Schizosaccharomyces pombe, and human cells. We demonstrate the application of NucleoATAC to a number of outstanding problems in chromatin biology, including analysis of sequence features underlying nucleosome positioning, promoter chromatin architecture across species, identification of transient changes in nucleosome occupancy and positioning during a dynamic cellular response, and integrated analysis of nucleosome occupancy and transcription factor binding. PMID:26314830
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.
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.
In architectural design education, students develop drawing, conceptual, and critical skills which are informed by their ability to reflect upon the production of ideas in design processes and in the urban, environmental, social, historical, and cultural context that define architecture and the built environment. Reflective actions and thinking…
Cuadrado, Ana; Remeseiro, Silvia; Graña, Osvaldo; Pisano, David G; Losada, Ana
Cohesin, which in somatic vertebrate cells consists of SMC1, SMC3, RAD21 and either SA1 or SA2, mediates higher-order chromatin organization. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these show reduced overlap with CCCTC-binding factor (CTCF) and are enriched at the regulatory regions of tissue-specific genes. Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1. Analyses of chromatin contacts at the Protocadherin (Pcdh) and Regenerating islet-derived (Reg) gene clusters, mostly expressed in brain and pancreas, respectively, revealed remarkable differences that correlate with the presence of cohesin. We could not detect significant changes in the chromatin contacts at the Pcdh locus when comparing brains from wild-type and SA1 null embryos. In contrast, reduced dosage of SA1 altered the architecture of the Reg locus and decreased the expression of Reg genes in the pancreas of SA1 heterozygous mice. Given the role of Reg proteins in inflammation, such reduction may contribute to the increased incidence of pancreatic cancer observed in these animals. PMID:25735743
Ian C. Welsh
Full Text Available Expression of Pitx2 on the left side of the embryo patterns left-right (LR organs including the dorsal mesentery (DM, whose asymmetric cell behavior directs gut looping. Despite the importance of organ laterality, chromatin-level regulation of Pitx2 remains undefined. Here, we show that genes immediately neighboring Pitx2 in chicken and mouse, including a long noncoding RNA (Pitx2 locus-asymmetric regulated RNA or Playrr, are expressed on the right side and repressed by Pitx2. CRISPR/Cas9 genome editing of Playrr, 3D fluorescent in situ hybridization (FISH, and variations of chromatin conformation capture (3C demonstrate that mutual antagonism between Pitx2 and Playrr is coordinated by asymmetric chromatin interactions dependent on Pitx2 and CTCF. We demonstrate that transcriptional and morphological asymmetries driving gut looping are mirrored by chromatin architectural asymmetries at the Pitx2 locus. We propose a model whereby Pitx2 auto-regulation directs chromatin topology to coordinate LR transcription of this locus essential for LR organogenesis.
Shih, Han-Yu; Krangel, Michael S.
The rearrangement of T and B lymphocyte antigen receptor loci occurs within a highly complex chromosomal environment and is orchestrated through complex mechanisms. Over the past decade, a large body of literature has highlighted the significance of chromatin architecture at antigen receptor loci in supporting the genomic assembly process: in preparation for recombination, these loci tend to contract and form multiple loops that shorten the distances between gene segments and facilitate recom...
Robinson, Philip W; Walther, Andreas; Faller, Christof; Braasch, Jonas
When sound reflects from an irregular architectural surface, it spreads spatially and temporally. Extensive research has been devoted to prediction and measurement of diffusion, but less has focused on its perceptual effects. This paper examines the effect of temporal diffusion on echo threshold. There are several notable differences between the waveform of a reflection identical to the direct sound and one from an architectural surface. The onset and offset are damped and the energy is spread in time; hence, the reflection response has a lower peak amplitude, and is decorrelated from the direct sound. The perceptual consequences of these differences are previously undocumented. Echo threshold tests are conducted with speech and music signals, using direct sound and a simulated reflection that is either identical to the direct sound or has various degrees of diffusion. Results indicate that for a speech signal, diffuse reflections are less easily detectable as a separate auditory event than specular reflections of the same total energy. For a music signal, no differences are observed between the echo thresholds for reflections with and without temporal diffusion. Additionally, echo thresholds are found to be shorter for speech than for music, and shorter for spatialized than for diotic presentation of signals. PMID:24116414
Fudenberg, Geoffrey; Getz, Gad; Meyerson, Matthew; Mirny, Leonid
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.
Jonathan S Adelstein
Full Text Available Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective 'hubs' in the brain--the anterior cingulate and precuneus--each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses.
Medrano-Fernández, Alejandro; Barco, Angel
The current view of neuroplasticity depicts the changes in the strength and number of synaptic connections as the main physical substrate for behavioral adaptation to new experiences in a changing environment. Although transcriptional regulation is known to play a role in these synaptic changes, the specific contribution of activity-induced changes to both the structure of the nucleus and the organization of the genome remains insufficiently characterized. Increasing evidence indicates that plasticity-related genes may work in coordination and share architectural and transcriptional machinery within discrete genomic foci. Here we review the molecular and cellular mechanisms through which neuronal nuclei structurally adapt to stimuli and discuss how the perturbation of these mechanisms can trigger behavioral malfunction. PMID:27595843
Finn, Elizabeth H; Misteli, Tom; Shachar, Sigal
Elucidating chromatin's 3D shape is critical to understanding its function, but the fine structure of chromatin domains remains poorly resolved. In a recent report in Nature, Boettiger et al. (2016) visualize chromatin in super-resolution, gaining unprecedented insight into chromatin architecture. PMID:26906730
Pantic, Igor; Dimitrijevic, Draga; Nesic, Dejan; Petrovic, Danica
We demonstrate that a proapoptotic chemical agent, oxidopamine, induces dose dependent changes in chromatin textural patterns which can be quantified using the Gray level co-occurrence matrix (GLCM) method. Peripheral blood (heparin-pretreated) samples were treated with oxidopamine (6-OHDA, 6-hydroxydopamine) to achieve effective concentrations of 100, 200 and 300µM. The samples were smeared on microscope slides and fixated in methanol. The smears were stained using a modification of Feulgen method for DNA visualization. For each stained smear, a sample of 30 lymphocyte chromatin structures were visualized and analyzed. This way, textural parameters for a total of 120 nuclei micrographs were calculated. For each chromatin structure, five different GLCM features were calculated: angular second moment, GLCM entropy, inverse difference moment, GLCM correlation, and GLCM variance. Oxidopamine induced the rise of the values of GLCM entropy and variance, and the reduction of angular second moment, correlation, and inverse difference moment. The trends for GLCM parameter changes were found to be highly significant (palgorithm might be successfully used in detection and evaluation of discrete early apoptotic structural changes in Feulgen-stained chromatin of peripheral blood lymphocytes that are not detectable using conventional microscopy/cell biology techniques. PMID:27424557
Robinson, Philip W.
This thesis addresses the effect of reflections from diffusive architectural surfaces on the perception of echoes and on auditory spatial resolution. Diffusive architectural surfaces play an important role in performance venue design for architectural expression and proper sound distribution. Extensive research has been devoted to the prediction and measurement of the spatial dispersion. However, previous psychoacoustic research on perception of reflections and the precedence effect has focused on specular reflections. This study compares the echo threshold of specular reflections, against those for reflections from realistic architectural surfaces, and against synthesized reflections that isolate individual qualities of reflections from diffusive surfaces, namely temporal dispersion and spectral coloration. In particular, the activation of the precedence effect, as indicated by the echo threshold is measured. Perceptual tests are conducted with direct sound, and simulated or measured reflections with varying temporal dispersion. The threshold for reflections from diffusive architectural surfaces is found to be comparable to that of a specular re ection of similar energy rather than similar amplitude. This is surprising because the amplitude of the dispersed re ection is highly attenuated, and onset cues are reduced. This effect indicates that the auditory system is integrating re ection response energy dispersed over many milliseconds into a single stream. Studies on the effect of a single diffuse reflection are then extended to a full architectural enclosure with various surface properties. This research utilizes auralizations from measured and simulated performance venues to investigate spatial discrimination of multiple acoustic sources in rooms. It is found that discriminating the lateral arrangement of two sources is possible at narrower separation angles when reflections come from at rather than diffusive surfaces. Additionally, subjective impressions are
Shieh, Grace S.
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.
The relationship between architecture and research has been barely discussed and by making use of critical reading this paper proposes to investigate how other disciplines started to use Research and Development (R&D) as part of their creative processes. In particular it explores how gastronomy has unfolded new R&D paths through the revolutionary work of three leading chefs: Ferrian Adria, Rene Redzepi and Grant Achatz, illustrating the deep impact that the use of R&D had in this field and ho...
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
Mirabella, Anne C; Foster, Benjamin M; Bartke, Till
The regulation of chromatin by epigenetic mechanisms plays a central role in gene expression and is essential for development and maintenance of cell identity and function. Aberrant chromatin regulation is observed in many diseases where it leads to defects in epigenetic gene regulation resulting in pathological gene expression programmes. These defects are caused by inherited or acquired mutations in genes encoding enzymes that deposit or remove DNA and histone modifications and that shape chromatin architecture. Chromatin deregulation often results in neurodevelopmental disorders and intellectual disabilities, frequently linked to physical and developmental abnormalities, but can also cause neurodegenerative diseases, immunodeficiency, or muscle wasting syndromes. Epigenetic diseases can either be of monogenic origin or manifest themselves as complex multifactorial diseases such as in congenital heart disease, autism spectrum disorders, or cancer in which mutations in chromatin regulators are contributing factors. The environment directly influences the epigenome and can induce changes that cause or predispose to diseases through risk factors such as stress, malnutrition or exposure to harmful chemicals. The plasticity of chromatin regulation makes targeting the enzymatic machinery an attractive strategy for therapeutic intervention and an increasing number of small molecule inhibitors against a variety of epigenetic regulators are in clinical use or under development. In this review, we will give an overview of the molecular lesions that underlie epigenetic diseases, and we will discuss the impact of the environment and prospects for epigenetic therapies. PMID:26188466
Even-Faitelson, Liron; Hassan-Zadeh, Vahideh; Baghestani, Zahra; Bazett-Jones, David P
Chromatin, once thought to serve only as a means to package DNA, is now recognized as a major regulator of gene activity. As a result of the wide range of methods used to describe the numerous levels of chromatin organization, the terminology that has emerged to describe these organizational states is often imprecise and sometimes misleading. In this review, we discuss our current understanding of chromatin architecture and propose terms to describe the various biochemical and structural states of chromatin. PMID:26223534
Full Text Available In a short article presented at a conference in New York City two years ago, Joan Ockman lucidly diagnosed the contemporary dilemma faced by architecture, i.e. how to insert itself between a pessimistic discourse that warns of the end of time, and an uncritical surrender to globalization. This dilemma is now universal(i. It applies to New York City, where in the same context Kenneth Frampton commented on the dystopia of an “oddly paranoid, rather ruthless, instrumental and resentful landscape”(ii, as well as to other cities around the world, especially in the Third World, where more difficult conditions permeate architectural practice, resulting in even more devastated landscapes. This article will discuss issues that relate to architectural practice and pedagogy, drawing on specific examples in the context of Beirut, Lebanon, and reflecting on the impact of‘architectural education’ and the transformations within the architectural profession in this context. One can no longer deny the negative impact of economics on a profession that has been, for the most part, idealistic in its approach to the built environment, but the responsibility of architects and architectural education, can no longer beminimized in assessing the problems that cities like Beirut face today. i The conference was organized at Columbia University, andpublished as The State of Architecture at the Beginning of the21st Century, New York: Monacelli Press, 2003. See JoanOckman’s “Criticism in the Age of Globalization” [78-9]ii “Brief Reflections on the Predicament of Urbanism” , ibidem[13
Darvishzadeh, Roshanak; Skidmore, Andrew; Atzberger, Clement; van Wieren, Sip
The retrieval of canopy biophysical variables is known to be affected by confounding factors such as plant type and background reflectance. The effects of soil type and plant architecture on the retrieval of vegetation leaf area index (LAI) from hyperspectral data were assessed in this study. In situ measurements of LAI were related to reflectances in the red and near-infrared and also to five widely used spectral vegetation indices (VIs). The study confirmed that the spectral contrast between leaves and soil background determines the strength of the LAI-reflectance relationship. It was shown that within a given vegetation species, the optimum spectral regions for LAI estimation were similar across the investigated VIs, indicating that the various VIs are basically summarizing the same spectral information for a given vegetation species. Cross-validated results revealed that, narrow-band PVI was less influenced by soil background effects (0.15 ≤ RMSE cv ≤ 0.56). The results suggest that, when using remote sensing VIs for LAI estimation, not only is the choice of VI of importance but also prior knowledge of plant architecture and soil background. Hence, some kind of landscape stratification is required before using hyperspectral imagery for large-scale mapping of vegetation biophysical variables.
Lazaro, Jose A.; Bock, Carlos; Polo, Victor; Martinez, Reynaldo I.; Prat, Josep
A highly scalable access architecture achieving high density and featuring resiliency, centralized light-generation control, remote amplification, and colorless optical network unit with reflective semiconductor optical amplifier (RSOA) for upstream modulation is presented and experimentally demonstrated. It is based on a user-single-fiber completely passive outside plant and provides broadband connections to >1000 users distributed along large distances. It is believed to represent an intermediate step toward metro-access convergence and offers flexible configurations covering high- and low-density population areas.
The Department of Architecture and Urban Planning at the Ethiopian Institute of Technology EiT of Mekelle University (MU is currently developing a research program in which the development of and reflection on design methods is a key research area. Within this framework, the present study is intends to be an introductory effort to guide future empirical research. The present study aims to describe the design process of architects, and introduces theoretical and technical frameworks. The integrated design paradigm as a system of inquiry within the spatial relationship strategy is framed.
The design studio environment has remained the same throughout the past century. As the Studio Culture Task Force of the American Institute of Architecture Students (AIAS) (Koch et al., 2006) noted, the ongoing changes in architecture education are not aligned with today׳s fast-changing world, especially in the context of architectural practice. The AIAS analyzed the design studio problem and expressed doubts on the effectiveness of current studio practices in providing adequate design-thinki...
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
Wolffe, Alan P
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
Williams-Hatala, E M; Hatala, K G; Hiles, S; Rabey, K N
Muscle attachment sites (entheses) on dry bones are regularly used by paleontologists to infer soft tissue anatomy and to reconstruct behaviors of extinct organisms. This method is commonly applied to fossil hominin hand bones to assess their abilities to participate in Paleolithic stone tool behaviors. Little is known, however, about how or even whether muscle anatomy and activity regimes influence the morphologies of their entheses, especially in the hand. Using the opponens muscles from a sample of modern humans, we tested the hypothesis that aspects of hand muscle architecture that are known to be influenced by behavior correlate with the size and shape of their associated entheses. Results show no consistent relationships between these behaviorally-influenced aspects of muscle architecture and entheseal morphology. Consequently, it is likely premature to infer patterns of behavior, such as stone tool making in fossil hominins, from these same entheses. PMID:27334440
Sailer, K.; Budgen, A.; Lonsdale, N; Turner, A.; A Penn
Evidence-based design is a practice that has emerged only relatively recently, inspired by a growing popularity of evidence-based approaches in other professions such as medicine. It has received greatest attention in design for the health sector, but has received less in office architecture, although this would seem not only to be beneficial for clients, but increasingly important in a changing business environment. This paper outlines the history and origins of evidence-based practice, its ...
de Wit, Elzo; Vos, Erica S M; Holwerda, Sjoerd J B; Valdes-Quezada, Christian; Verstegen, Marjon J A M; Teunissen, Hans; Splinter, Erik; Wijchers, Patrick J; Krijger, Peter H L; de Laat, Wouter
CCCTC-binding factor (CTCF) is an architectural protein involved in the three-dimensional (3D) organization of chromatin. In this study, we assayed the 3D genomic contact profiles of a large number of CTCF binding sites with high-resolution 4C-seq. As recently reported, our data also suggest that ch
Yu, Sonia; Yang, Fan; Shen, Wen H
The eukaryotic genome is packaged in the three-dimensional nuclear space by forming loops, domains, and compartments in a hierarchical manner. However, when duplicated genomes prepare for segregation, mitotic cells eliminate topologically associating domains and abandon the compartmentalized structure. Alongside chromatin architecture reorganization during the transition from interphase to mitosis, cells halt most DNA-templated processes such as transcription and repair. The intrinsically condensed chromatin serves as a sophisticated signaling module subjected to selective relaxation for programmed genomic activities. To understand the elaborate genome-epigenome interplay during cell cycle progression, the steady three-dimensional genome requires a time scale to form a dynamic four-dimensional and a more comprehensive portrait. In this review, we will dissect the functions of critical chromatin architectural components in constructing and maintaining an orderly packaged chromatin environment. We will also highlight the importance of the spatially and temporally conscious orchestration of chromatin remodeling to ensure high-fidelity genetic transmission. PMID:27098512
Hnilicová, Jarmila; Staněk, David
There are numerous data suggesting that two key steps in gene expression—transcription and splicing influence each other closely. For a long time it was known that chromatin modifications regulate transcription, but only recently it was shown that chromatin and histone modifications play a significant role in pre-mRNA splicing. Here we summarize interactions between splicing machinery and chromatin and discuss their potential functional significance. We focus mainly on histone acetylation and...
Gelato, Kathy A; Fischle, Wolfgang
Chromosomes in eukaryotic cell nuclei are not uniformly organized, but rather contain distinct chromatin elements, with each state having a defined biochemical structure and biological function. These are recognizable by their distinct architectures and molecular components, which can change in response to cellular stimuli or metabolic requirements. Chromatin elements are characterized by the fundamental histone and DNA components, as well as other associated non-histone proteins and factors. Post-translational modifications of histone proteins in particular often correlate with a specific chromatin structure and function. Patterns of histone modifications are implicated as having a role in directing the level of chromatin compaction, as well as playing roles in multiple functional pathways directing the readout of distinct regions of the genome. We review the properties of various chromatin elements and the apparent links of histone modifications with chromatin organization and functional output. PMID:18225984
Braae, Ellen Marie
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....
Chevrot, C.; Teyssié, D.; Verge, P.; Goujon, L.; Tran-Van, F.; Vidal, F.; Aubert, P. H.; Peralta, S.; Sauques, L.
A promising alternative of multi-layered devices showing electrochromic properties results from the design of a self-supported semi-interpenetrating polymer network (semi-IPN) including an electronic conductive polymer (ECP) formed within. The formation of the ECP in the network has already been described by oxidative polymerization using iron trichloride as an oxidant and leading to conducting semi-IPN with mixed electronic and ionic conductivities as well as convenient mechanical properties. This presentation relates to the elaboration of such semi-IPN using polyethyleneoxide (PEO) network or a PEO/NBR (Nitrile Butadiene Rubber) IPN in which a linear poly (3,4-ethylenedioxythiophene) (PEDOT) is formed symmetrically and selectively as very thin layers very next to the two main faces of the film matrix. PEO/PEDOT semi-IPNs lead to interesting optical reflective properties in the IR between 0.8 and 25 μm. Reflectance contrasts up to 35 % is observed when, after swelling in an ionic liquid, a low voltage is applied between the two main faces of the film. However the low flexibility and brittleness of the film and a slow degradation in air at temperature up from 60°C prompted to replace the PEO matrix by a flexible PEO/NBR IPN one. Indeed, the combination of NBR and PEO in an IPN leads to materials possessing flexible properties, good ionic conductivity at 25°C as well as a better resistance to thermal ageing. Finally, NBR/PEO/PEDOT semi-IPNs allow observing comparable reflectance contrast in the IR range than those shown by PEO/PEDOT semi-IPNs.
Moreau, Julien; Anderskouv, Kresten; Boldreel, Lars Ole;
The Upper Cretaceous-Danian chalk is well exposed in the 14 km long coastal cliff of Stevns Klint (eastern Denmark). The cliff is a world renowned for its spectacular exposure of the Cretaceous-Palaeogene boundary. Based on regional geological knowledge of the field and cores, the characteristics...... completed with the acquisition of an extensive set of subsurface data. The data include high resolution 2D multichannel seismics onshore and offshore, a seismic refraction profile, two entirely cored boreholes including wireline logs, GPR cross-hole tomography, thermographic analysis, etc. We intend...... to compile and merge the geological and geophysical datasets to investigate the variation of the Chalk Group properties and their signature in the subsurface. In this communication, the seismic reflection data are being analysed. Very high resolution litho-, bio- and cyclostratigraphy can be correlated...
ZHANGYi; OUYANGZhenqian; 等
The chromatin folding patterns in air and liquid were studied by atomic force microscopy(AFM),A gentle water-air interface method was adopted to spread chromatin from interphase nucleus of chicken erythrocyte.The chromatin was absorbed on APS-mica surface and studied with AFM,Beads-on a-string were observed and many higher-order structrues such as superbeads with dimensions 40-60nm in diameter and 4-7nm in height were found to string together to make chromation fibers.When sample spreading and absorbing time were shortened.higher-order chromatin fibers with 60-120nm in width were observed in air as well as under water environment.These chromatin structures may reflect chromatin folding patterns in the living cells.
Full Text Available In the nucleus of eukaryotic cells, histone proteins organize the linear genome into a functional and hierarchical architecture. In this paper, we use the crystal structures of the nucleosome core particle, B-DNA and the globular domain of H5 linker histone to build the first all-atom model of compact chromatin fibers. In this 3D jigsaw puzzle, DNA bending is achieved by solving an inverse kinematics problem. Our model is based on recent electron microscopy measurements of reconstituted fiber dimensions. Strikingly, we find that the chromatin fiber containing linker histones is a polymorphic structure. We show that different fiber conformations are obtained by tuning the linker histone orientation at the nucleosomes entry/exit according to the nucleosomal repeat length. We propose that the observed in vivo quantization of nucleosomal repeat length could reflect nature's ability to use the DNA molecule's helical geometry in order to give chromatin versatile topological and mechanical properties.
Khuong, Mai T.; Fei, Jia; Ishii, Haruhiko; Kadonaga, James T.
Chromatin consists of nucleosomes as well as nonnucleosomal histone-containing particles. Here we describe the prenucleosome, which is a stable conformational isomer of the nucleosome that associates with ~80 bp DNA. Prenucleosomes are formed rapidly upon the deposition of histones onto DNA and can be converted into canonical nucleosomes by an ATP-driven chromatin assembly factor such as ACF. Different lines of evidence reveal that there are prenucleosome-sized DNA-containing particles with histones in the upstream region of active promoters. Moreover, p300 acetylates histone H3K56 in prenucleosomes but not in nucleosomes, and H3K56 acetylation is found at active promoters and enhancers. These findings therefore suggest that there may be prenucleosomes or prenucleosome-like particles in the upstream region of active promoters. More generally, we postulate that prenucleosomes or prenucleosome-like particles are present at dynamic chromatin, whereas canonical nucleosomes are at static chromatin. PMID:26767995
Alabert, Constance; Groth, Anja
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...
LiuWang; AihuaZheng; LingYi; ChongrenXu; MingxiaoDing; HongkuiDeng
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.
W. Fischle; D. Schwarzer; Mootz, H.
Analysing post-translational modifications of histone proteins as they occur within chromatin is challenging due to their large number and chemical diversity. A major step forward has now been achieved by using split intein chemistry to engineer functionalized histones within cells.
Terms to be familiar with before you start to solve the test: chromatin, nucleases, sucrose density gradient centrifugation, melting point, gel electrophoresis, ethidium bromide, autoradiography, Southern blotting, Northern blotting, Sanger sequencing, restriction endonucleases, exonucleases, linker DNA, chloroform extraction, nucleosomes,…
Hnilicová, Jarmila; Staněk, David
Roč. 2, č. 3 (2011), s. 182-188. ISSN 1949-1034 R&D Projects: GA ČR GAP305/10/0424; GA AV ČR KAN200520801 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromatin * exon * alternative splicing * transcription * snRNP Subject RIV: EB - Genetics ; Molecular Biology
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.
Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Brian T. Glazer; Krepski, Sean T.; Emerson, David
Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respecti...
ZhenHe Fan; Yan Qiao
In the China merchants property 2013 green architectural design competition, feature of this award-winning program is the design method based on the principles of passive priority and comprehensive utilization of full life cycle. The passive priority can be achieved by building form derived from the simulation and analysis of wind environment, improvement of the building envelope insulation and the dehumidification of fresh air, the use of solar energy. The full life cycle utilization can be accomplished by the combination of exhibition and residents’ leisure activities, and the integration with local cultural tradition, thereby improving energy efficiency and the utilization of the building.
Bancaud, Aurelien; Barbi, Maria; Wagner, Gaudeline; Allemand, Jean-Francois; Mozziconacci, Julien; Lavelle, Christophe; Croquette, Vincent; Victor, Jean-Marc; Prunell, Ariel; Viovy, Jean-Louis
Magnetic tweezers are used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large amount of supercoiling without much change in length. This behavior is quantitatively described by a molecular model of the chromatin 3-D architecture. In this model, we assume the existence of a dynamic equilibrium between three conformations of the nucleosome, which are determined by the crossing status of the entry/exit DNAs (positive, null or negative). Torsional strain, in displacing that equilibrium, extensively reorganizes the fiber architecture. The model explains a number of long-standing topological questions regarding DNA in chromatin, and may provide the ground to better understand the dynamic binding of most chromatin-associated proteins.
The 'ATLAS Metadata Interface' framework (AMI) has been developed in the context of ATLAS, one of the largest scientific collaborations. AMI can be considered to be a mature application, since its basic architecture has been maintained for over 10 years. In this paper we describe briefly the architecture and the main uses of the framework within the experiment (TagCollector for release management and Dataset Discovery). These two applications, which share almost 2000 registered users, are superficially quite different, however much of the code is shared and they have been developed and maintained over a decade almost completely by the same team of 3 people. We discuss how the architectural principles established at the beginning of the project have allowed us to continue both to integrate the new technologies and to respond to the new metadata use cases which inevitably appear over such a time period.
Gassler, Nikolaus; Kopitz, Jürgen; Tehrani, Arman;
-CoA synthetase 5 pattern correlate with conversion of intestinal epithelial cells to a gastric phenotype. These results suggest that deranged acyl-CoA synthetase 5 expression, synthesis, and activity are closely related to the state of villus architecture and epithelial homeostasis in human small intestine.......Several disorders of the small intestine are associated with disturbances in villus architecture. Thus, an understanding of the molecular mechanisms associated with the differentiation of villi represents an important step in the improvement of the understanding of small intestinal pathology...
Barkal, Amira A.; Srinivasan, Sharanya; Hashimoto, Tatsunori; Gifford, David K.; Sherwood, Richard I.
Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding.
Barkal, Amira A.; Srinivasan, Sharanya; Gifford, David K.; Sherwood, Richard I.; Hashimoto, Tatsunori Benjamin
Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding.
Amira A Barkal
Full Text Available Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding.
Barkal, Amira A.; Srinivasan, Sharanya; Hashimoto, Tatsunori; Gifford, David K.; Sherwood, Richard I.
Using a nuclease-dead Cas9 mutant, we show that Cas9 reproducibly induces chromatin accessibility at previously inaccessible genomic loci. Cas9 chromatin opening is sufficient to enable adjacent binding and transcriptional activation by the settler transcription factor retinoic acid receptor at previously unbound motifs. Thus, we demonstrate a new use for Cas9 in increasing surrounding chromatin accessibility to alter local transcription factor binding. PMID:27031353
How the same DNA sequences can function in the three-dimensional architecture of interphase nucleus, fold in the very compact structure of metaphase chromosomes and go precisely back to the original interphase architecture in the following cell cycle remains an unresolved question to this day. The strategy used to address this issue was to analyze the correlations between chromosome architecture and the compositional patterns of DNA sequences spanning a size range from a few hundreds to a few thousands Kilobases. This is a critical range that encompasses isochores, interphase chromatin domains and boundaries, and chromosomal bands. The solution rests on the following key points: 1) the transition from the looped domains and sub-domains of interphase chromatin to the 30-nm fiber loops of early prophase chromosomes goes through the unfolding into an extended chromatin structure (probably a 10-nm “beads-on-a-string” structure); 2) the architectural proteins of interphase chromatin, such as CTCF and cohesin sub-units, are retained in mitosis and are part of the discontinuous protein scaffold of mitotic chromosomes; 3) the conservation of the link between architectural proteins and their binding sites on DNA through the cell cycle explains the “mitotic memory” of interphase architecture and the reversibility of the interphase to mitosis process. The results presented here also lead to a general conclusion which concerns the existence of correlations between the isochore organization of the genome and the architecture of chromosomes from interphase to metaphase. PMID:26619076
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.
Toft, Tanya Søndergaard
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 to...... 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....
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...
The main statistical distributions applicable to the analysis of genome architecture and genome tracks are briefly discussed and critically assessed. Although the observed features in distributions of element lengths can be equally well fitted by the different statistical approximations, the interpretation of observed regularities may strongly depend on the chosen scheme. We discuss the possible evolution scenarios and describe the main characteristics obtained with different distributions. The expression for the assessment of levels in hierarchical chromatin folding is derived and the quantitative measure of genome architecture inhomogeneity is suggested. This theory provides the ground for the regular statistical study of genome architecture and genome tracks.
Clara S Chan
Full Text Available Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to
Chan, Clara S.; McAllister, Sean M.; Leavitt, Anna H.; Glazer, Brian T.; Krepski, Sean T.; Emerson, David
Microbes form mats with architectures that promote efficient metabolism within a particular physicochemical environment, thus studying mat structure helps us understand ecophysiology. Despite much research on chemolithotrophic Fe-oxidizing bacteria, Fe mat architecture has not been visualized because these delicate structures are easily disrupted. There are striking similarities between the biominerals that comprise freshwater and marine Fe mats, made by Beta- and Zetaproteobacteria, respectively. If these biominerals are assembled into mat structures with similar functional morphology, this would suggest that mat architecture is adapted to serve roles specific to Fe oxidation. To evaluate this, we combined light, confocal, and scanning electron microscopy of intact Fe microbial mats with experiments on sheath formation in culture, in order to understand mat developmental history and subsequently evaluate the connection between Fe oxidation and mat morphology. We sampled a freshwater sheath mat from Maine and marine stalk and sheath mats from Loihi Seamount hydrothermal vents, Hawaii. Mat morphology correlated to niche: stalks formed in steeper O2 gradients while sheaths were associated with low to undetectable O2 gradients. Fe-biomineralized filaments, twisted stalks or hollow sheaths, formed the highly porous framework of each mat. The mat-formers are keystone species, with nascent marine stalk-rich mats comprised of novel and uncommon Zetaproteobacteria. For all mats, filaments were locally highly parallel with similar morphologies, indicating that cells were synchronously tracking a chemical or physical cue. In the freshwater mat, cells inhabited sheath ends at the growing edge of the mat. Correspondingly, time lapse culture imaging showed that sheaths are made like stalks, with cells rapidly leaving behind an Fe oxide filament. The distinctive architecture common to all observed Fe mats appears to serve specific functions related to chemolithotrophic Fe
S. Henikoff (Steven); F.G. Grosveld (Frank)
textabstractOn 11 to 13 March 2013, BioMed Central will be hosting its inaugural conference, Epigenetics & Chromatin: Interactions and Processes, at Harvard Medical School, Cambridge, MA, USA. Epigenetics & Chromatin has now launched a special article series based on the general themes of the confer
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)
Radu, L.; Mihailescu, I.; Radu, S.; Gazdaru, D.
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.
Roloff, Tim C; Nuber, Ulrike A
Epigenetics is a term that has changed its meaning with the increasing biological knowledge on developmental processes. However, its current application to stem cell biology is often imprecise and is conceptually problematic. This article addresses two different subjects, the definition of epigenetics and chromatin states of stem and differentiated cells. We describe mechanisms that regulate chromatin changes and provide an overview of chromatin states of stem and differentiated cells. Moreover, a modification of the current epigenetics definition is proposed that is not restricted by the heritability of gene expression throughout cell divisions and excludes translational gene expression control. PMID:15819395
Bancaud, Aurelien; Silva, Natalia Conde e; Barbi, Maria; Wagner, Gaudeline; Allemand, Jean-Francois; Mozziconacci, Julien; Lavelle, Christophe; Croquette, Vincent; Victor, Jean-Marc; Prunell, Ariel; Viovy, Jean-Louis
Magnetic tweezers are used to study the mechanical response under torsion of single nucleosome arrays reconstituted on tandem repeats of 5S positioning sequences. Regular arrays are extremely resilient and can reversibly accommodate a large amount of supercoiling without much change in length. This behavior is quantitatively described by a molecular model of the chromatin 3-D architecture. In this model, we assume the existence of a dynamic equilibrium between three conformations of the nucle...
The characteristics of epigenetic control, including the potential for long-lasting, stable effects on gene expression that outlive an initial transient signal, could be of singular importance for post-mitotic neurons, which are subject to changes with short- to long-lasting influence on their activity and connectivity. Persistent changes in chromatin structure are thought to contribute to mechanisms of epigenetic inheritance. Recent advances in chromatin biology offer new avenues to investig...
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
Vietri Rudan, M.
The organisation of the DNA inside eukaryotic cell nuclei is not random. Rather than being intermingled with one another, chromosomes are compacted in a hierarchical manner which is conserved throughout eukaryote evolution. Topological domains have recently emerged as key architectural building blocks of chromosomes in complex genomes. This thesis aimed to explore the evolutionary dynamics of chromatin architecture in order to shed light on its functional relevance and on how architectural pr...
Yusufaly, Tahir I.
This dissertation discuss two recent efforts, via a unique combination of structural bioinformatics and density functional theory, to unravel some of the details concerning how molecular machinery within the eukaryotic cell nucleus controls chromatin architecture. The first, a study of the 5-methylation of cytosine in 5'-CG-3' : 5'-CG-3' base-pair steps, reveals that the methyl groups roughen the local elastic energy landscape of the DNA. This enhances the probability of the canonical B-DNA structure transitioning into the undertwisted A-like and overtwisted C-like forms seen in nucleosomes, or looped segments of DNA bound to histones. The second part focuses on the formation of salt bridges between arginine residues in histones and phosphate groups on the DNA backbone. The arginine residues are ob- served to apply a tunable mechanical load to the backbone, enabling precision-controlled activation of DNA deformations.
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 with...
This dissertation examines the structure and structural transitions of chromatin in relation to DNA damage. The ability of intact and histone H1 depleted chromatin fibers to fold into higher ordered structures in vitro was examined following DNA photodamage introduced by two different agents. (1) 254-nm UV radiation and (2) trimethylpsoralen (plus near-UV radiation). Both agents are highly specific for DNA and form adducts predicted to cause different degrees of distortion in the DNA helix. The salt-induced structural transitions of intact and histone H1 depleted chromatin fibers were monitored by both analytical ultracentrifugation and light scattering. Our results show that even in the presence of extremely large, nonphysiological amounts of photodamage by either agent the ability of chromatin to fold into higher ordered structures is not affected. The compact, 30 nm fiber must therefore be able to accommodate a large amount of DNA damage without any measurable changes in the overall size or degree of compaction of this structure. The distribution of pyrimidine dimers was mapped at the single nucleotide level in nucleosome core DNA from UV-irradiated mononucleosomes, chromatin fibers, and human cells in culture using the 3' → 5' exonuclease activity of T4 DNA polymerase
Jeans, C; Thelen, M P; Noy, A
In eukaryotic cells, DNA is packaged as chromatin, a highly ordered structure formed through the wrapping of the DNA around histone proteins, and further packed through interactions with a number of other proteins. In order for processes such as DNA replication, DNA repair, and transcription to occur, the structure of chromatin must be remodeled such that the necessary enzymes can access the DNA. A number of remodeling enzymes have been described, but our understanding of the remodeling process is hindered by a lack of knowledge of the fine structure of chromatin, and how this structure is modulated in the living cell. We have carried out single molecule experiments using atomic force microscopy (AFM) to study the packaging arrangements in chromatin from a variety of cell types. Comparison of the structures observed reveals differences which can be explained in terms of the cell type and its transcriptional activity. During the course of this project, sample preparation and AFM techniques were developed and optimized. Several opportunities for follow-up work are outlined which could provide further insight into the dynamic structural rearrangements of chromatin.
The DNA in the eukaryotic nucleus is organized into a complex DNA-protein structure called chromatin. The basic repeating unit of chromatin is the nucleosome, which consists of 147 bp of DNA wrapped around a histone protein octamer. The nucleosomes form a “beads on a string” structure, which can be folded into higherorder structures that allow an extensive degree of DNA compaction. This compaction is so effective that 2 meters of DNA can fit into the human cell nucleus with a ...
Ben-Haïm, E; Lesne, A; Victor, J M
This paper focuses on mechanical aspects of chromatin biological functioning. Within a basic geometric modeling of the chromatin assembly, we give a complete set of elastic constants (twist and bend persistence lengths, stretch modulus and twist-stretch coupling constant) of the so-called 30-nm chromatin fiber, in terms of DNA elastic properties and geometric properties of the fiber assembly. The computation naturally embeds the fiber within a current analytical model known as the "extensible wormlike rope," allowing a straightforward prediction of the force-extension curves. We show that these elastic constants are strongly sensitive to the linker length, up to 1 bp, or equivalently to its twist, and might locally reach very low values, yielding a highly flexible and extensible domain in the fiber. In particular, the twist-stretch coupling constant, reflecting the chirality of the chromatin fiber, exhibits steep variations, and sign changes when the linker length is varied. We argue that this tunable elasticity might be a key feature for chromatin function, for instance, in the initiation and regulation of transcription. PMID:11735982
Vassetzky, Y; Hair, A; Méchali, M
A dynamic change in the organization of different gene domains transcribed by RNA polymerase I, II, or III occurs during the progression from quiescent [pre-midblastula transition (pre-MBT)] to active (post-MBT) embryos during Xenopus development. In the rDNA, c-myc, and somatic 5S gene domains, a transition from random to specific anchorage to the nuclear matrix occurs when chromatin domains become active. The keratin gene domain was also randomly associated to the nuclear matrix before MBT, whereas a defined attachment site was found in keratinocytes. In agreement with this specification, ligation-mediated (LM)-PCR genomic footprinting carried out on the subpopulation of 5S domains specifically attached to the matrix reveals the hallmarks of determined chromatin after the midblastula transition. In contrast, the same analysis performed on the total 5S gene population does not reveal specific chromatin organization, validating the use of nuclear matrix fractionation to unveil active chromatin domains. These data provide a means for the determination of active chromosomal territories in the embryo and emphasize the role of nuclear architecture in regulated gene expression during development. PMID:10859171
International audience In this chapter, we introduce an additional, yet essential, concept in describing software architectures : architecture constraints. We explain the precise role of these entities and their importance in object-oriented, component-based or service-oriented software engi-neering. We then describe the way in which they are specified and interpreted. An architect can define architecture constraints and then associate them to architectural descriptions to limit their stru...
how recognising the autonomy of architecture, not as an esoteric concept but as a valid source of information in a pragmatic design practice, may help us overcome the often-proclaimed dichotomy between formal autonomy and a societally committed architecture. It follows that in architectural education...
Altmeyer, Matthias; Lukas, Jiri
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....
Lara-Astiaso, David; Weiner, Assaf; Lorenzo-Vivas, Erika; Zaretsky, Irina; Jaitin, Diego Adhemar; David, Eyal; Keren-Shaul, Hadas; Mildner, Alexander; Winter, Deborah; Jung, Steffen; Friedman, Nir; Amit, Ido
Chromatin modifications are crucial for development, yet little is known about their dynamics during differentiation. Hematopoiesis provides a well-defined model to study chromatin state dynamics, however technical limitations impede profiling of homogeneous differentiation intermediates. We developed a high sensitivity indexing-first chromatin immunoprecipitation approach (iChIP) to profile the dynamics of four chromatin modifications across 16 stages of hematopoietic differentiation. We ide...
Huang, Jialiang; Marco, Eugenio; Pinello, Luca; Yuan, Guo-Cheng
Genome-wide mapping of three dimensional chromatin organization is an important yet technically challenging task. To aid experimental effort and to understand the determinants of long-range chromatin interactions, we have developed a computational model integrating Hi-C and histone mark ChIP-seq data to predict two important features of chromatin organization: chromatin interaction hubs and topologically associated domain (TAD) boundaries. Our model accurately and robustly predicts these feat...
Agosto, Luis M.; Matthew Gagne; Henderson, Andrew J.
Chromatin influences Human Immunodeficiency Virus (HIV) integration and replication. This review highlights critical host factors that influence chromatin structure and organization and that also impact HIV integration, transcriptional regulation and latency. Furthermore, recent attempts to target chromatin associated factors to reduce the HIV proviral load are discussed.
Groth, Anja; Rocha, Walter; Verreault, Alain;
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...
Radu, Liliana, E-mail: email@example.com [V. Babes National Institute, Department of Molecular Genetics and Radiobiology (Romania); Mihailescu, I. [National Institute for Lasers, Plasma and Radiation Physics, Department of Lasers (Romania); Gazdaru, Doina [Faculty of Physics, Bucharest University, Department of Biophysics (Romania); Preoteasa, V. [V. Babes National Institute, Department of Molecular Genetics and Radiobiology (Romania)
The effects of three UV excimer laser radiations, with wavelengths of 193, 248 and 282 nm respectively, on the structure of chromatin (the complex of deoxyribonucleic acid with proteins that exists in eukaryotic cells nuclei) were investigated. The chromatin was extracted from livers of Winstar rats. The spectroscopic methods used are: fluorescence (Foerster) resonance energy transfer (FRET), time resolved fluorescence and steady-state fluorescence. A chromatin deoxyribonucleic acid radiolysis, a chromatin proteins damage and a change of the global chromatin structure on lasers action were indicated by this study. It exists some small differences between the actions of these three laser radiations.
Dunlop Malcolm G
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
Alcock, Gordon Lindsay
This paper documents 1st semester student reflections on “learning to learn” in a team-based PBL environment with quantitative and qualitative student reflective feedback on the learning gains of 60 Architectural Technology and Construction Management students at VIA University College, Denmark. It...... contrasts the students’ self-assessment in a range of ‘product’ skills such as Revit, Structural Design, Mathematics of construction, Technical Installations; as well as ‘process’ competencies such as ‘Working in a team’, Sharing knowledge, Maintaining a portfolio and Reflecting ON learning and FOR learning...
Aguilar-Arnal, Lorena; Sassone-Corsi, Paolo
The molecular circadian clock orchestrates the daily cyclical expression of thousands of genes. Disruption of this transcriptional program leads to a variety of pathologies, including insomnia, depression and metabolic disorders. Circadian rhythms in gene expression rely on specific chromatin transitions which are ultimately coordinated by the molecular clock. As a consequence, a highly plastic and dynamic circadian epigenome can be delineated across different tissues and cell types. Intrigui...
De Gobbi Marco
Full Text Available Abstract Background In self-renewing, pluripotent cells, bivalent chromatin modification is thought to silence (H3K27me3 lineage control genes while 'poising' (H3K4me3 them for subsequent activation during differentiation, implying an important role for epigenetic modification in directing cell fate decisions. However, rather than representing an equivalently balanced epigenetic mark, the patterns and levels of histone modifications at bivalent genes can vary widely and the criteria for identifying this chromatin signature are poorly defined. Results Here, we initially show how chromatin status alters during lineage commitment and differentiation at a single well characterised bivalent locus. In addition we have determined how chromatin modifications at this locus change with gene expression in both ensemble and single cell analyses. We also show, on a global scale, how mRNA expression may be reflected in the ratio of H3K4me3/H3K27me3. Conclusions While truly 'poised' bivalently modified genes may exist, the original hypothesis that all bivalent genes are epigenetically premarked for subsequent expression might be oversimplistic. In fact, from the data presented in the present work, it is equally possible that many genes that appear to be bivalent in pluripotent and multipotent cells may simply be stochastically expressed at low levels in the process of multilineage priming. Although both situations could be considered to be forms of 'poising', the underlying mechanisms and the associated implications are clearly different.
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...... the obligation to prepare students to perform in a profession that is largely defined by forces outside that discipline. It will be proposed that the autonomy of architecture can be understood as a unique kind of information: as architecture’s self-reliance or knowledge-about itself. A knowledge 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...
Chromatin architecture plays an important role in DNA-template based processes, including transcription, DNA damage repair, replication, and apoptosis. Post-translational modification of histones and non-histone proteins through actions of histone acetyltransferase (HAT) and histone deacetylase (HDAC) regulates chromatin conformation, resulting in the control of accessibility of proteins to target sites. Some of these proteins are involved in cell cycle regulation and DNA damage repair process (ie. Rb, E2F1, p21, p53 and BRCA 1 and 2). However, the mechanism underlying the role of chromatin modification on cellular intrinsic radiation sensitivity is poorly understood. Ataxia-telangiectasia mutated (ATM), the product of the gene mutated in cells from patients with the radiation sensitivity syndrome of ataxia-telangiectasia, has been shown to be involved in multiple DNA damage-induced signal transduction pathways. Previously, we have observed that ATM interacts with histone deacetylase HDAC1 both in vivo and in vitro and its complex exhibits deacetylase activity in response to ionizing radiation. Further studies have suggested that ATM is involved in the regulation of p53 via post-translational modification. Using isogenic AT cell lines, which show radiation sensitivity differences (Do 0.7 and 1.4 Gy), we performed microarray analyses of gene expression at various intervals following irradiation. These data provide evidence for distinctive ATM-dependent or -independent radiation-mediated gene regulation patterns
Mondal, Tanmoy; Rasmussen, Markus; Pandey, Gaurav Kumar; Isaksson, Anders; Kanduri, Chandrasekhar
Noncoding RNA (ncRNA) constitutes a significant portion of the mammalian transcriptome. Emerging evidence suggests that it regulates gene expression in cis or trans by modulating the chromatin structure. To uncover the functional role of ncRNA in chromatin organization, we deep sequenced chromatin-associated RNAs (CARs) from human fibroblast (HF) cells. This resulted in the identification of 141 intronic regions and 74 intergenic regions harboring CARs. The intronic and intergenic CARs show s...
Miyanari, Yusuke; Ziegler-Birling, Céline; Torres-Padilla, Maria-Elena
The spatiotemporal organization of genomes in the nucleus is an emerging key player to regulate genome function. Live imaging of nuclear organization dynamics would be a breakthrough toward uncovering the functional relevance and mechanisms regulating genome architecture. Here, we used transcription activator-like effector (TALE) technology to visualize endogenous repetitive genomic sequences. We established TALE-mediated genome visualization (TGV) to label genomic sequences and follow nuclear positioning and chromatin dynamics in cultured mouse cells and in the living organism. TGV is highly specific, thus allowing differential labeling of parental chromosomes by distinguishing between single-nucleotide polymorphisms (SNPs). Our findings provide a framework to address the function of genome architecture through visualization of nuclear dynamics in vivo. PMID:24096363
Our objective was to evaluate alterations in sperm chromatin structure in men occupationally exposed to a mixture of organophosphorus pesticides (OP) because these alterations have been proposed to compromise male fertility and offspring development. Chromatin susceptibility to in situ acid-induced denaturation structure was assessed by the sperm chromatin structure assay (SCSA). Urinary levels of alkylphosphates (DAP) were used to assess exposure. Diethylthiophosphate (DETP) was the most frequent OP metabolite found in urine samples indicating that compounds derived from thiophosphoric acid were mainly used. Chromatin structure was altered in most samples. About 75% of semen samples were classified as having poor fertility potential (>30% of Percentage of DNA Fragmentation Index [DFI%]), whereas individuals without OP occupational exposure showed average DFI% values of 9.9%. Most parameters of conventional semen analysis were within normality except for the presence of immature cells (IGC) in which 82% of the samples were above reference values. There were significant direct associations between urinary DETP concentrations and mean DFI and SD-DFI but marginally (P = 0.079) with DFI%, after adjustment for potential confounders, including IGC. This suggests that OP exposure alters sperm chromatin condensation, which could be reflected in an increased number of cells with greater susceptibility to DNA denaturation. This study showed that human sperm chromatin is a sensitive target to OP exposure and may contribute to adverse reproductive outcomes. Further studies on the relevance of protein phosphorylation as a possible mechanism by which OP alter sperm chromatin are required
Full Text Available In addition to the superficial visual similarities between the architectural theories of the Silesian-born, seventeenth-century Dutch mathematician Nicolaus Goldmann and the early nineteenth-century French architect Jean-Nicolas-Louis Durand, there is a more profound interconnection: their use of the grid. This article evaluates the relation between the two theories and argues how Durand could have been influenced by Goldmann’s writings. It turns out to be more than likely that the two were linked by Durand´s German pupils who brought the tradition of German eighteenth-century architectural theory with them. This corpus was nourished by Leonhard Christoph Sturm´s ‘Goldmannic’ architecture.
Gupta, Noopur Agarwal; Becker, Annette; Jost, K Laurence;
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...
Perišić, Ognjen; Schlick, Tamar
While the genetic information is contained in double helical DNA, gene expression is a complex multilevel process that involves various functional units, from nucleosomes to fully formed chromatin fibers accompanied by a host of various chromatin binding enzymes. The chromatin fiber is a polymer composed of histone protein complexes upon which DNA wraps, like yarn upon many spools. The nature of chromatin structure has been an open question since the beginning of modern molecular biology. Many experiments have shown that the chromatin fiber is a highly dynamic entity with pronounced structural diversity that includes properties of idealized zig-zag and solenoid models, as well as other motifs. This diversity can produce a high packing ratio and thus inhibit access to a majority of the wound DNA. Despite much research, chromatin's dynamic structure has not yet been fully described. Long stretches of chromatin fibers exhibit puzzling dynamic behavior that requires interpretation in the light of gene expression patterns in various tissue and organisms. The properties of chromatin fiber can be investigated with experimental techniques, like in vitro biochemistry, in vivo imagining, and high-throughput chromosome capture technology. Those techniques provide useful insights into the fiber's structure and dynamics, but they are limited in resolution and scope, especially regarding compact fibers and chromosomes in the cellular milieu. Complementary but specialized modeling techniques are needed to handle large floppy polymers such as the chromatin fiber. In this review, we discuss current approaches in the chromatin structure field with an emphasis on modeling, such as molecular dynamics and coarse-grained computational approaches. Combinations of these computational techniques complement experiments and address many relevant biological problems, as we will illustrate with special focus on epigenetic modulation of chromatin structure. PMID:27345617
Denker, Annette; de Laat, Wouter
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 genome
Gong Hong WEI; De Pei LIU; Chih Chuan LIANG
The eukaryotic genome is organized into functionally and structurally distinct domains, representing regulatory units for gene expression and chromosome behavior. DNA sequences that mark the border between adjacent domains are the insulators or boundary elements, which are required in maintenance of the function of different domains. Some insulators need others enable to play insulation activity. Chromatin domains are defined by distinct sets of post-translationally modified histones. Recent studies show that these histone modifications are also involved in establishment of sharp chromatin boundaries in order to prevent the spreading of distinct domains. Additionally, in some loci, the high-order chromatin structures for long-range looping interactions also have boundary activities, suggesting a correlation between insulators and chromatin loop domains. In this review, we will discuss recent progress in the field of chromatin domain boundaries.
Perišić, Ognjen; Schlick, Tamar
While the genetic information is contained in double helical DNA, gene expression is a complex multilevel process that involves various functional units, from nucleosomes to fully formed chromatin fibers accompanied by a host of various chromatin binding enzymes. The chromatin fiber is a polymer composed of histone protein complexes upon which DNA wraps, like yarn upon many spools. The nature of chromatin structure has been an open question since the beginning of modern molecular biology. Many experiments have shown that the chromatin fiber is a highly dynamic entity with pronounced structural diversity that includes properties of idealized zig-zag and solenoid models, as well as other motifs. This diversity can produce a high packing ratio and thus inhibit access to a majority of the wound DNA. Despite much research, chromatin’s dynamic structure has not yet been fully described. Long stretches of chromatin fibers exhibit puzzling dynamic behavior that requires interpretation in the light of gene expression patterns in various tissue and organisms. The properties of chromatin fiber can be investigated with experimental techniques, like in vitro biochemistry, in vivo imagining, and high-throughput chromosome capture technology. Those techniques provide useful insights into the fiber’s structure and dynamics, but they are limited in resolution and scope, especially regarding compact fibers and chromosomes in the cellular milieu. Complementary but specialized modeling techniques are needed to handle large floppy polymers such as the chromatin fiber. In this review, we discuss current approaches in the chromatin structure field with an emphasis on modeling, such as molecular dynamics and coarse-grained computational approaches. Combinations of these computational techniques complement experiments and address many relevant biological problems, as we will illustrate with special focus on epigenetic modulation of chromatin structure.
Christensen, Henrik Bærbak; Hansen, Klaus Marius
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....
Full Text Available Architecture today, no longer reflects the limits of experimentation and innovation. An extremely low-tech art whose field of possibilities consists of choosing and using that which has already been done in the past. It is because of this that the key skill a designer should have is the ability to recognize the complexity in forms around them: cities have the widest programming opportunities for architecture, in the two-way relationship that is established from the city that takes form in architecture and an architecture that finds its place in the contemporary city. Thus, architecture has its foundation in hospitality, an element that differentiates it significantly from the design.
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.
Bardram, Jakob; Christensen, Henrik Bærbak; Hansen, Klaus Marius
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......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...
Bardram, Jakob Eyvind; Christensen, Henrik Bærbak; Hansen, Klaus Marius
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......' concerns with respect to a system under development. An architectural prototype is primarily a learning and communication vehicle used to explore and experiment with alternative architectural styles, features, and patterns in order to balance different architectural qualities. The use of architectural...... prototypes in the development process is discussed, and we argue that such prototypes can play a role throughout the entire process. The use of architectural prototypes is illustrated by three distinct cases of creating software systems. We argue that architectural prototyping can provide key insights that...
Brand architecture is a structure of brands that specifies the roles of different brands of a company and the logical relationships between the brands, and is designed to take advantage of the collective force of different brands and maximize the brand equity of the company. To improve SINOPEC’s brand architecture in future requires a systematic thinking from four aspects: the driving roles of brand elements, the collective force of brands, brand extension capabilities and integration of acquired businesses.%品牌架构用来描述企业中不同品牌的角色以及品牌之间的逻辑关系，目的是发挥不同品牌的协同效应，最大限度地壮大企业的品牌资产。未来中国石化品牌架构的完善，需要从品牌元素的驱动作用、品牌之间的协同作用、品牌的延伸能力、收购业务的整合四个方面进行系统思考。
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.
Victor Jean Marc
Full Text Available Abstract Background Understanding the mechanical properties of chromatin is an essential step towards deciphering the physical rules of gene regulation. In the past ten years, many single molecule experiments have been carried out, and high resolution measurements of the chromatin fiber stiffness are now available. Simulations have been used in order to link those measurements with structural cues, but so far no clear agreement among different groups has been reached. Results We revisit here some of the most precise experimental results obtained with carefully reconstituted fibers. Conclusions We show that the mechanical properties of the chromatin fiber can be quantitatively accounted for by the stiffness of the DNA molecule and the 3D structure of the chromatin fiber.
The authors have previously shown that exposure of responding cells to vitamin A leads to profound modifications of chromatin structure as revealed by an increased susceptibility to DNase I digestion, modified patterns of histone acetylation, and impaired synthesis of a nonhistone chromosomal protein. The present results show that these effects are most probably due to the direct interaction between retinol and chromatin, and analysis of mononucleosomes and higher oligomers obtained from retinol-treated cells shows that retinol is indeed tightly bound to chromatin. Enzymatic digestions of vitamin A containing nucleosomes with proteinase K, phospholipase C, and phospholipase A2 support a model where the final binding of retinol to chromatin is mediated by a lipoprotein: the recognition of the binding sites on DNA being dictated by the proteic component while the hydrophobic retinol is solubilized in the fatty acid moiety
Kooistra, Susanne M; van den Boom, Vincent; Thummer, Rajkumar P;
to dimethyl sulfoxide (DMSO) or after LIF withdrawal and display increased colony formation. UTF1 KD ES cells display extensive chromatin decondensation, reflected by a dramatic increase in nucleosome release on micrococcal nuclease (MNase) treatment and enhanced MNase sensitivity of UTF1 target...
Ozer, Gungor; Luque, Antoni; Schlick, Tamar
The structure of chromatin, affected by many factors from DNA linker lengths to posttranslational modifications, is crucial to the regulation of eukaryotic cells. Combined experimental and computational methods have led to new insights into its structural and dynamical features, from interactions due to the flexible core histone tails of the nucleosomes to the physical mechanism driving the formation of chromosomal domains. Here we present a perspective of recent advances in chromatin modelin...
Recouvreux, Pierre; Lavelle, Christophe; Barbi, Maria; Conde e Silva, Natalia; Le Cam, Eric; Victor, Jean-Marc; Viovy, Jean-Louis
Genomic DNA in eukaryotic cells is organized in supercoiled chromatin fibers, which undergo dynamic changes during such DNA metabolic processes as transcription or replication. Indeed, DNA-translocating enzymes like polymerases produce physical constraints in vivo. We used single-molecule micromanipulation by magnetic tweezers to study the response of chromatin to mechanical constraints in the same range as those encountered in vivo. We had previously shown that under positive torsional const...
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
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. PMID:25363760
Full Text Available Evidence suggests that human sperm chromatin anomalies adversely affect reproductive outcomesand infertile men possess substantially amount of sperm with chromatin anomalies than fertilemen.Routine semen analysis evaluates parameters such as sperm motility and morphology, but doesnot examine the nuclear DNA integrity of spermatozoa. It has been suggested that altered nuclearchromatin structure or damaged DNA in spermatozoa could modify the special cellular functionsof human spermatozoa, and thereby affect the fertility potential. Intra-cytoplasmic sperm injection(ICSI bypass the barriers to fertilization for such a sperm, then the effect of chromatin anomalies onthe development remains a concern. Therefore, it is essential to develop and use accurate diagnostictests, which may provide better prognostic capabilities than the standard sperm assessments. Thisreview discusses our current understanding of the structure and organization of sperm DNA,the different procedures for assessment of sperm chromatin anomalies including comet assay,Chromomycin A3 (CMA3, sperm chromatin structure assay (SCSA, acridine orange test (AOT,terminal TdT-mediated dUTP-nick-end labelling (TUNEL assay, aniline blue and sperm chromatindispersion (SCD test and the impact of chromatin anomalies on reproductive outcome.
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, consequently presenting it either as the negation of all form of architecture or as the critique of 'classical' architectural forms. Against this ‘appropriation’, i.e. this reductive reading and the subse...
Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning
and recovery through the architecture framing eating experiences, this article examines, from a theoretical perspective, two less debated concepts relating to hospitality called food design and architectural theatricality. In architectural theory the nineteenth century German architect Gottfried...... Semper 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...
Randell, B.; Treleaven, P.C.
This book is a collection of course papers which discusses the latest (1982) milestone of electronic building blocks and its effect on computer architecture. Contributions range from selecting a VLSI process technology to Japan's Fifth Generation Computer Architecture. Contents, abridged: VLSI and machine architecture. Graphic design aids: HED and FATFREDDY. On the LUCIFER system. Clocking of VLSI circuits. Decentralised computer architectures for VLSI. Index.
Pereira, Marcia A.
Using Schon's concepts and definition of reflective practice, this article elaborates a model used to analyze the author's own processes of "reflection-in-action" and "reflection-on-action" in teaching first-year architectural students. Emphasizes the importance of the concept of "role-frame" in informing the whole reflective process. (EV)
Under the theme Architecture in the Network Society, participants were invited to focus on the dialog and sharing of knowledge between architects and other disciplines and to reflect on, and propose, new methods in the design process, to enhance and improve the impact of information technology...... on architecture. This conference and the past history of eCAADe is an example on establishing a social network for the sharing of knowledge regarding the use of computers in architectural education and research....
Erickson, Mary; Delahunt, Michael
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…
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.
Wei, Juan; Czapla, Luke; Grosner, Michael A; Swigon, David; Olson, Wilma K
Topological constraints placed on short fragments of DNA change the disorder found in chain molecules randomly decorated by nonspecific, architectural proteins into tightly organized 3D structures. The bacterial heat-unstable (HU) protein builds up, counter to expectations, in greater quantities and at particular sites along simulated DNA minicircles and loops. Moreover, the placement of HU along loops with the "wild-type" spacing found in the Escherichia coli lactose (lac) and galactose (gal) operons precludes access to key recognition elements on DNA. The HU protein introduces a unique spatial pathway in the DNA upon closure. The many ways in which the protein induces nearly the same closed circular configuration point to the statistical advantage of its nonspecificity. The rotational settings imposed on DNA by the repressor proteins, by contrast, introduce sequential specificity in HU placement, with the nonspecific protein accumulating at particular loci on the constrained duplex. Thus, an architectural protein with no discernible DNA sequence-recognizing features becomes site-specific and potentially assumes a functional role upon loop formation. The locations of HU on the closed DNA reflect long-range mechanical correlations. The protein responds to DNA shape and deformability—the stiff, naturally straight double-helical structure—rather than to the unique features of the constituent base pairs. The structures of the simulated loops suggest that HU architecture, like nucleosomal architecture, which modulates the ability of regulatory proteins to recognize their binding sites in the context of chromatin, may influence repressor-operator interactions in the context of the bacterial nucleoid. PMID:25385626
Garcia-Macias, Vanesa; Martinez-Pastor, Felipe; Alvarez, Mercedes; Garde, Jose Julian; Anel, Enrique; Anel, Luis; de Paz, Paulino
Abnormal chromatin condensation is not detected using classical techniques for sperm analysis. SCSA has demonstrated its usefulness in sperm chromatin analysis in several species (human, bull, stallion and boar). In this work, we studied sperm samples from red deer, ram and dog to analyze the differentiation of chromatin structure applying SCSA in epididymal and ejaculated spermatozoa. Epididymal samples were obtained from the caput, corpus and cauda by means of cuts, and ejaculated ones were obtained by electroejaculation (deer), artificial vagina (ram) and digital manipulation (dog). SCSA results suggested different critical points in sperm maturation (spermatozoa with loose chromatin to more condensed chromatin) among species: from corpus to cauda in ram and from caput to corpus in deer and dog. Moreover, we also detected differences in ruminants and dog, reflected in the appearance of SCSA plots. Indeed, ram and deer samples rendered two peaks within the sperm main population (sperm with condensed chromatin), whereas only one was detected in dog. Although some differences were observed between cauda and ejaculated samples, SCSA parameters indicated good chromatin condensation, making these samples suitable for germplasm banking. Some species-dependent modifications in the analysis of the results may be necessary to take full advantage of its analytical power. PMID:16790270
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.
Wu, Xiaoyun; Shi, Zhen; Cui, Mingxue; Han, Min; Ruvkun, Gary
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. PMID:22412383
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)
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.
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 H2O-D2O 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
Arifulin E. A.
Full Text Available Aim. The ultrastructural aspect of replicating chromatin organization is a matter of dispute. Here, we have analyzed the ultrastructural organization of replication foci using prematurely condensed chromosomes (PCC. Methods. To investigate the ultrastructure of replicating chromatin, we have used correlative light and electron microscopy as well as immunogold staining. Results. Replication in PCC occurs in the gaps between condensed chromatin domains. Using correlative light and electron microscopy, we observed that the replication foci contain decondensed chromatin as well as 80 and 130 nm globules, those were also found in condensed non-replicating chromatin domains. Using immunogolding, we demonstrated that DNA replication in S-phase PCC occurs in loose chromatin on the periphery of dense chromatin domains. Conclusion. Replication in PCC occurred in the decondensed chromatin neighboring the condensed chromatin without formation of special structures.
Tvedebrink, Tenna Doktor Olsen
This PhD thesis is motived by a personal interest in the theoretical, practical and creative qualities of architecture. But also a wonder and curiosity about the cultural and social relations architecture represents through its occupation with both the sciences and the arts. Inspired by present...... initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture, is...... the current building of a series of Danish ‘super hospitals’ and an increased focus among architectural practices on research-based knowledge produced with the architectural sub-disciplines Healing Architecture and Evidence-Based Design. The problem is that this research does not focus on patient...
Ramachandran, Srinivas; Henikoff, Steven
Precise positioning of nucleosomes around regulatory sites is achieved by the action of chromatin remodelers, which use the energy of ATP to slide, evict or change the composition of nucleosomes. Chromatin remodelers act to bind nucleosomes, disrupt histone-DNA interactions and translocate the DNA around the histone core to reposition nucleosomes. Hence, remodeling is expected to involve nucleosomal intermediates with a structural organization that is distinct from intact nucleosomes. We describe the identification of a partially unwrapped nucleosome structure using methods that map histone-DNA contacts genome-wide. This alternative nucleosome structure is likely formed as an intermediate or by-product during nucleosome remodeling by the RSC complex. Identification of the loss of histone-DNA contacts during chromatin remodeling by RSC in vivo has implications for the regulation of transcriptional initiation. PMID:26933790
Recouvreux, Pierre; Lavelle, Christophe; Barbi, Maria; Conde e Silva, Natalia; Le Cam, Eric; Victor, Jean-Marc; Viovy, Jean-Louis
Genomic DNA in eukaryotic cells is organized in supercoiled chromatin fibers, which undergo dynamic changes during such DNA metabolic processes as transcription or replication. Indeed, DNA-translocating enzymes like polymerases produce physical constraints in vivo. We used single-molecule micromanipulation by magnetic tweezers to study the response of chromatin to mechanical constraints in the same range as those encountered in vivo. We had previously shown that under positive torsional constraints, nucleosomes can undergo a reversible chiral transition toward a state of positive topology. We demonstrate here that chromatin fibers comprising linker histones present a torsional plasticity similar to that of naked nucleosome arrays. Chromatosomes can undergo a reversible chiral transition toward a state of positive torsion (reverse chromatosome) without loss of linker histones. PMID:21641318
Dame, Remus T; Tark-Dame, Mariliis
Bacterial genomes are functionally organized and compactly folded into a structure referred to as bacterial chromatin or the nucleoid. An important role in genome folding is attributed to Nucleoid-Associated Proteins, also referred to as bacterial chromatin proteins. Although a lot of molecular insight in the mechanisms of operation of these proteins has been generated in the test tube, knowledge on genome organization in the cellular context is still lagging behind severely. Here, we discuss important advances in the understanding of three-dimensional genome organization due to the application of Chromosome Conformation Capture and super-resolution microscopy techniques. We focus on bacterial chromatin proteins whose proposed role in genome organization is supported by these approaches. Moreover, we discuss recent insights into the interrelationship between genome organization and genome activity/stability in bacteria. PMID:26942688
According to their physical characteristics, protons and ion beams promise a revolution in cancer radiotherapy. Curing protocols however reflect rather the empirical knowledge than experimental data on DNA repair. This especially holds for the spatio-temporal organization of repair processes in the context of higher-order chromatin structure—the problematics addressed in this work. The consequences for the mechanism of chromosomal translocations are compared for gamma rays and proton beams. - Highlights: ► The majority of DSBs are repaired individually close to the sites of their origin. ► Decondensation of damaged chromatin domains can potentiate clustering of lesions. ► DSB clustering might increase the risk of chromatin translocation. ► Distances of lesions and higher-order chromatin structure influence DSB clustering. ► The conclusions seem to hold both for DSB damage caused by γ-radiation and protons
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 firstname.lastname@example.org Based on the repetitive architecture from the "building boom" 1960...... to 1973 it is discussed how architects can handle these Danish element and montage buildings through the transformation to upgraded aesthetical, functional and energy efficient architecture. The method used is analysis of cases, parallels to literature studies and producer interviews. This analysis...... compares "best practice" in Denmark and "best practice" in Austria. The modern architects accepted the fact that industrialized architecture told the storey of repetition and monotonous as basic condition. This article aims to explain that architecture can be thought as a complex and diverse design through...
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...... reassembly on nascent DNA strands. The aim of this review is to discuss how histones - new and old - are handled at the replication fork, highlighting new mechanistic insights and revisiting old paradigms.......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...
Full Text Available Yeqing Angela Yang,1 Jung Kim,1 Jindan Yu1,21Division of Hematology/Oncology, Department of Medicine, 2Robert H Lurie Comprehensive Cancer Center, Northwestern University, Feinberg School of Medicine, Chicago, IL, USAAbstract: In recent years, facilitated by rapid technological advances, we are becoming more adept at probing the molecular processes, which take place in the nucleus, that are crucial for the hierarchical regulation and organization of chromatin architecture. With an unprecedented level of resolution, a detailed atlas of chromosomal structures (histone displacement, variants, modifications, chromosome territories, and DNA looping and mechanisms underlying their establishment, provides invaluable insight into physiological as well as pathological phenomena. In this review, we will focus on prostate cancer, a prevalent malignancy in men worldwide, and for which a curative treatment strategy is yet to be attained. We aim to catalog the most frequently observed oncogenic alterations associated with chromatin conformation, while emphasizing the TMPRSS2-ERG fusion, which is found in more than one-half of prostate cancer patients and its functions in compromising the chromatin landscape in prostate cancer.Keywords: chromatin conformation, ERG, prostate cancer
Reflected, artistic practices and design-based research are drastically expanding fields within architectural academia. However, the interest in uniting theory and practice is not entirely new. Just a few decades ago, before a ‘death of theory’ was proclaimed, questions of architectural epistemol...... – an embracing pursuit of an architectural ethos....
Avgeriou, Paris; Stal, Michael; Hilliard, Rich
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 first Web extra at http://youtu.be/wUGHvocfix0 is an audio interview in which Davide Falessi speaks with guest editors Paris Avgeriou and Rich Hilliard about the importance of architecture sustainabil...
Vogel, Oliver; Chughtai, Arif
As a software architect you work in a wide-ranging and dynamic environment. You have to understand the needs of your customer, design architectures that satisfy both functional and non-functional requirements, and lead development teams in implementing the architecture. And it is an environment that is constantly changing: trends such as cloud computing, service orientation, and model-driven procedures open up new architectural possibilities. This book will help you to develop a holistic architectural awareness and knowledge base that extends beyond concrete methods, techniques, and technologi
Kiib, Hans; Marling, Gitte; Hansen, Peter Mandal
How can architecture promote the enriching experiences of the tolerant, the democratic, and the learning city - a city worth living in, worth supporting and worth investing in? Catalyst Architecture comprises architectural projects, which, by virtue of their location, context and their combination...... of programs, have a role in mediating positive social and/or cultural development. In this sense, we talk about architecture as a catalyst for: sustainable adaptation of the city’s infrastructure appropriate renovation of dilapidated urban districts strengthening of social cohesiveness in the city...
This paper demystifies reflective practice on teaching by focusing on the idea of reflection itself and how it has been conceived by two philosophers, Plato and Irigaray. It argues that reflective practice has become a standardized method of defining the teacher in teacher education and teacher accreditation systems. It explores how practices of…
Chen, Hsiuyi V.; Rando, Oliver J.
In this issue of Molecular Cell, van Bemmel and colleagues (2013) report the genome-wide mapping of 42 novel chromatin factors, systematically identifying new components of the various chromatin domains present in fly cells. PMID:23438859
Bennink, M.L.; Pope, L.H.; Leuba, S.H.; Grooth, de B.G.; Greve, J.
Here we observe the formation of a single chromatin fibre using optical tweezers. A single -DNA molecule was suspended between two micron-sized beads, one held by a micropipette and the other in an optical trap. The constrained DNA molecule was incubated with Xenopus laevis egg extract in order to r
Bey, Till; Jamge, Suraj; Klemme, Sonja; Komar, Dorota Natalia; Gall, Le Sabine; Mikulski, Pawel; Schmidt, Martin; Zicola, Johan; Berr, Alexandre
In January 2016, the first Epigenetic and Chromatin Regulation of Plant Traits conference was held in Strasbourg, France. An all-star lineup of speakers, a packed audience of 130 participants from over 20 countries, and a friendly scientific atmosphere contributed to make this conference a meetin
Helin, Kristian; Dhanak, Dashyant
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 ...
Grøntved, Lars; Hager, Gordon L
but also to the glucocorticoid receptor (GR), as these receptors share many similarities regarding interaction with, and remodeling of, chromatin. Both receptors can bind nucleosomal DNA and have accordingly been described as pioneering factors. However recent genomic approaches (ChIP-seq and DHS...
With the support of National Natural Science Foundation of China, BGI, the largest genomics organization in the world, and Peking University Shenzhen Hospital, published online in Nature Geneticsics that the study on frequent mutations of chromatin remodeling genes in transitional cell carcinoma （TCC） of thebladder on August 8th, 2011. Their study provides a valuable genetic basis for future studies on TCC,
Fog, Cathrine K; Jensen, Klaus T; Lund, Anders Henrik
Chromatin-modifying proteins mold the genome into areas that are accessible for transcriptional activity and areas that are transcriptionally silent. This epigenetic gene regulation allows for different transcriptional programs to be conducted in different cell types at different timepoints-despi...
Khalifa, T A A; Rekkas, C A; Lymberopoulos, A G; Sioga, A; Dimitriadis, I; Papanikolaou, Th
The structural stability of transcriptionally inert paternal chromatin is of vital importance for the fertilization process and early embryonic development. Accordingly, a series of eight experiments were conducted during a 7-month period to investigate: (1) effects of bull breed, individuality, successive ejaculations, semen quality characteristics (SQC), semen dilution rates and hypothermic storage of semen in a Tris-egg yolk extender on incidence of sperm nuclear chromatin instability (NCI), and (2) effects of the interaction between variation of NCI within a frozen ejaculate and variation of oocytes quality due to maturation time and/or season on the efficiency of in vitro embryo production (IVEP). Semen samples were collected once a week from six bulls using an AV and only ejaculates (n=220) of >0.30x10(9) sperm/ml and >or=60% motility were used. NCI was measured by: (1) detection of lysine-rich histones in sperm chromatin using aniline blue staining, (2) sperm susceptibility to acid-induced nuclear DNA denaturation in situ using acridine orange test, and (3) sperm susceptibility to nuclear chromatin decondensation (NCD). Bovine oocytes (n=695) were matured in vitro for 18 or 24 h, fertilized after sperm selection through a swim-up procedure and cultured for 72 h. The results showed that the 2nd ejaculates were superior to the 1st ones with respect to chromatin stability. Dilution of semen to 49.67+/-8.56x10(6) sperm/ml (1:19) decreased resistance of sperm to NCD. Cooling of semen had no significant effect on chromatin stability. Cryopreservation of semen augmented sperm vulnerability to DNA denaturation. Improvement of SQC (semen volume, sperm motility, velocity, viability and morphological normalcy) was generally concomitant with increase of sperm resistance to NCI. While Blonde d'Aquitaine bulls had a resistance to NCD higher than Limousine bulls in fresh semen, the former showed a greater susceptibility to DNA denaturation than the latter in cooled semen
Lystbæk, Christian Tang
Reflection has moved from the margins to the mainstream in supervision. Notions of reflection have become well established since the late 1980s. These notions have provided useful framing devices to help conceptualize some important processes in guidance and counseling. However, some applications...... previously associated with reflection and an exploration of alternative conceptions that view reflection within the context of settings which have a more group- and team-based orientation. Drawing on an action research project on health care supervision, the paper questions whether we should reject earlier...... views of reflection, rehabilitate them in order to capture broader connotations or move to new ways of regarding reflection that are more in keeping with not only reflective but also emotive, normative and formative views on supervision. The paper presents a critical perspective on supervision that...
Poletto, Marco; Pasquero, Claudia
This is a manual investigating the subject of urban ecology and systemic development from the perspective of architectural design. It sets out to explore two main goals: to discuss the contemporary relevance of a systemic practice to architectural design, and to share a toolbox of informational...... design protocols developed to describe the city as a territory of self-organization. Collecting together nearly a decade of design experiments by the authors and their practice, ecoLogicStudio, the book discusses key disciplinary definitions such as ecologic urbanism, algorithmic architecture, bottom......-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...
Fargion, D.; Gaug, M.; Oliva, P.
Magic Telescope may observe and reveal at horizons lights from air-shower Cherenkov reflections. The ground, the sea, the cloudy sky (below the mountain) may reflect PeVs-EeV UHECR Cherenkov lights observable by MAGIC telescopes. Even rarest UHE neutrino skimming the atmosphere or skimming the Earth may induce upward-horizontal airshowers: a new Neutrino Astronomy. These fluorescence signals or the Cherenkov reflections in upper cloudy sky may flash in correlated BL-Lac or GRB shining at oppo...
Wu, Jingyi; Huang, Bo; Chen, He; Yin, Qiangzong; Liu, Yang; Xiang, Yunlong; Zhang, Bingjie; Liu, Bofeng; Wang, Qiujun; Xia, Weikun; Li, Wenzhi; Li, Yuanyuan; Ma, Jing; Peng, Xu; Zheng, Hui; Ming, Jia; Zhang, Wenhao; Zhang, Jing; Tian, Geng; Xu, Feng; Chang, Zai; Na, Jie; Yang, Xuerui; Xie, Wei
In mammals, extensive chromatin reorganization is essential for reprogramming terminally committed gametes to a totipotent state during preimplantation development. However, the global chromatin landscape and its dynamics in this period remain unexplored. Here we report a genome-wide map of accessible chromatin in mouse preimplantation embryos using an improved assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) approach with CRISPR/Cas9-assisted mitochondrial DNA depletion. We show that despite extensive parental asymmetry in DNA methylomes, the chromatin accessibility between the parental genomes is globally comparable after major zygotic genome activation (ZGA). Accessible chromatin in early embryos is widely shaped by transposable elements and overlaps extensively with putative cis-regulatory sequences. Unexpectedly, accessible chromatin is also found near the transcription end sites of active genes. By integrating the maps of cis-regulatory elements and single-cell transcriptomes, we construct the regulatory network of early development, which helps to identify the key modulators for lineage specification. Finally, we find that the activities of cis-regulatory elements and their associated open chromatin diminished before major ZGA. Surprisingly, we observed many loci showing non-canonical, large open chromatin domains over the entire transcribed units in minor ZGA, supporting the presence of an unusually permissive chromatin state. Together, these data reveal a unique spatiotemporal chromatin configuration that accompanies early mammalian development. PMID:27309802
The search for the clean and the perfect in our cities is reflected in the spatial exclusion of certain people, especially those on the margin of society. New immigrants, prostitutes and voyageurs are part of those communities often placed in invaluable districts. The concept of the city with a rich diversity of cultures and social backgrounds becomes increasingly a fairy tale, far from reality.As curator of the 4th International Architecture Biennale in Rotterdam (2010) Kees Christiaanse rev...
Steiner, Florian A; Henikoff, Steven
Centromeric chromatin is distinguished primarily by nucleosomes containing the histone variant cenH3, which organizes the kinetochore that links the chromosome to the spindle apparatus. Whereas budding yeast have simple 'point' centromeres with single cenH3 nucleosomes, and fission yeast have 'regional' centromeres without obvious sequence specificity, the centromeres of most organisms are embedded in highly repetitive 'satellite' DNA. Recent studies have revealed a remarkable diversity in centromere chromatin organization among different lineages, including some that have lost cenH3 altogether. We review recent progress in understanding point, regional and satellite centromeres, as well as less well-studied centromere types, such as holocentromeres. We also discuss the formation of neocentromeres, the role of pericentric heterochromatin, and the structure and composition of the cenH3 nucleosome. PMID:25956076
Barbi, Maria; Mozziconacci, Julien; Victor, Jean-Marc; Wong, Hua; Lavelle, Christophe
The ability of cells to pack, use and duplicate DNA remains one of the most fascinating questions in biology. To understand DNA organization and dynamics, it is important to consider the physical and topological constraints acting on it. In the eukaryotic cell nucleus, DNA is organized by proteins acting as spools on which DNA can be wrapped. These proteins can subsequently interact and form a structure called the chromatin fibre. Using a simple geometric model, we propose a general method for computing topological properties (twist, writhe and linking number) of the DNA embedded in those fibres. The relevance of the method is reviewed through the analysis of magnetic tweezers single molecule experiments that revealed unexpected properties of the chromatin fibre. Possible biological implications of these results are discussed. PMID:24098838
Tvedebrink, Tenna Doktor Olsen; Fisker, Anna Marie; Kirkegaard, Poul Henning
German architect Gottfried Semper developed a theory on the “four elements of Architecture” tracing the origin of architecture back to the rise of the early human settlement and the creation of fire. With the notion ‘hearth’ as the first motive in architecture and the definition of three enclosing...... motives; mounding, enclosure and roof, Semper linked the cultural and social values of the primordial fireplace with the order and shape of architecture. He claimed that any building ever made was nothing but a variation of the first primitive shelters erected around the fireplace, and that the three...... enclosing motives existed only as defenders of the “sacred flame”. In that way Semper developed the idea that any architectural scenery can be described, analyzed and explained by understanding the contextual, symbolic and social values of how the four basic motives of hearth, mounding, enclosure, and roof...
Barbi, Maria; Mozziconacci, Julien; Victor, Jean-Marc; Wong, Hua; Lavelle, Christophe
The ability of cells to pack, use and duplicate DNA remains one of the most fascinating questions in biology. To understand DNA organization and dynamics, it is important to consider the physical and topological constraints acting on it. In the eukaryotic cell nucleus, DNA is organized by proteins acting as spools on which DNA can be wrapped. These proteins can subsequently interact and form a structure called the chromatin fibre. Using a simple geometric model, we propose a general method fo...
Renthal, William; Nestler, Eric J.
Alterations in gene expression are implicated in the pathogenesis of several neuropsychiatrie disorders, including drug addiction and depression, increasing evidence indicates that changes in gene expression in neurons, in the context of animal models of addiction and depression, are mediated in part by epigenetic mechanisms that alter chromatin structure on specific gene promoters. This review discusses recent findings from behavioral, molecular, and bioinformatic approaches that are being u...
Filippova, Darya; Patro, Rob; Duggal, Geet; Kingsford, Carl
Chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types and conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally-relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across various r...
Filippova, Darya; Patro, Rob; Duggal, Geet; Kingsford, Carl
Recent chromosome conformation capture experiments have led to the discovery of dense, contiguous, megabase-sized topological domains that are similar across cell types and conserved across species. These domains are strongly correlated with a number of chromatin markers and have since been included in a number of analyses. However, functionally-relevant domains may exist at multiple length scales. We introduce a new and efficient algorithm that is able to capture persistent domains across va...
Shirey, David E.
The following thesis is comprised of a pair of projects focused on the making of architecture through the concept of framing. The work was conducted at the Academia dÃ ÂArchitettura in Mendrisio, Switzerland, under the direction of Peter Zumthor, Miguel Kreisler and Myriam Sterling, emphasizing the relationship between ordered structures and contextual propriety. The making of architecture is inherently most pure when approached as the subtraction of unnecessary elements and a distillation ...
Maurin, Bernard; Motro, René
The basic idea for a textile architecture project originates during early meetings between the architect and the engineer. The morphologic richness of such projects is provided by the varying curvatures of shapes, in contradiction with a classical straight line and orthogonal architecture. However the rules of construction are quite different in terms of realisation and of mechanical behaviour: textile membranes are subjected to a pre-stress conferring them their rigidity, and a major objecti...
Research focuses on the recognition of the disposition of natural environment, which serves as an inspiration for cultural creation as it has always been in the history of architecture. Modern mathematical model of fractal geometry has been used to understand patterns occurring in the surrounding. The comparative analysis has been conducted between the abstract mathematical model and architectural composition in the view of contemporary cognitive paradigms. In conclusion, a hypothesis of a ne...
An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of...
Donovan, Elizabeth; Holder, Anna
This paper will reflect on understandings of architectural pedagogy and the integration of sustainability into architectural design education. This is framed within an understanding of the construction industry’s role in the production of waste. Despite the complexity of global environmental crises......, architectural educators have the opportunity to do more to address this. We begin with a discussion of contemporary literature and policy concerning education for sustainability in architecture, articulating the particular approaches in development within higher education. This is then compared with critical...... understandings of how architects synthesise different types of knowledge while designing, raising questions about the ‘match’ between educational experiences and subsequent behaviours in practice. Taking an example from Denmark, we outline the approach of Aarhus School of Architecture, where sustainability...
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)
Johnson, Graham D; Jodar, Meritxell; Pique-Regi, Roger; Krawetz, Stephen A
Nuclear remodeling to a condensed state is a hallmark of spermatogenesis. This is achieved by replacement of histones with protamines. Regions retaining nucleosomes may be of functional significance. To determine their potential roles, sperm from wild type and transgenic mice harboring a single copy insert of the human protamine cluster were subjected to Micrococcal Nuclease-seq. CENTIPEDE, a hierarchical Bayesian model, was used to identify multiple spatial patterns, "footprints", of MNase-seq reads along the sperm genome. Regions predicted by CENTIPEDE analysis to be bound by a regulatory factor in sperm were correlated with genomic landmarks and higher order chromatin structure datasets to identify potential roles for these factors in regulating either prior or post spermatogenic, i.e., early embryonic events. This approach linked robust endogenous protamine transcription and transgene suppression to its chromatin environment within topologically associated domains. Of the candidate enhancer-bound regulatory proteins, Ctcf, was associated with chromatin domain boundaries in testes and embryonic stem cells. The continuity of Ctcf binding through the murine germline may permit rapid reconstitution of chromatin organization following fertilization. This likely reflects its preparation for early zygotic genome activation and comparatively accelerated preimplantation embryonic development program observed in mouse as compared to human and bull. PMID:27184706
Bayramian, Andrew James; Manes, Kenneth; Deri, Robert; Erlandson, Al; Caird, John; Spaeth, Mary
An optical gain architecture includes a pump source and a pump aperture. The architecture also includes a gain region including a gain element operable to amplify light at a laser wavelength. The gain region is characterized by a first side intersecting an optical path, a second side opposing the first side, a third side adjacent the first and second sides, and a fourth side opposing the third side. The architecture further includes a dichroic section disposed between the pump aperture and the first side of the gain region. The dichroic section is characterized by low reflectance at a pump wavelength and high reflectance at the laser wavelength. The architecture additionally includes a first cladding section proximate to the third side of the gain region and a second cladding section proximate to the fourth side of the gain region.
Full Text Available Around 1968 we saw the birth of a new architectural theory as the conjunction of architectural history and politically engaged architectural criticism. Not the aesthetics of architecture, but architecture itself in its structural relations with social life became the focus of attention. As a result of this development, it is no longer possible to study architectural history without a critical reflection on the method of the study itself and without a grade of interdisciplinarity. Traditional methods of historiography and iconography have been replaced by new approaches configured by psychoanalysis, deconstruction, cultural studies etc. Appropriation has become the proof of criticality both in architectural theory and in design; however, the understanding of the concepts and methods of other disciplines is basically metaphorical. The problem for a school of architecture lies not in the ‘criticality’ of the kind of architectural theory we described as emerging from the spirit of 1968, but in its discursive nature. The disciplinary specificity of architecture resists a discursive approach, and architectural students frequently question the usefulness of theory which undermines the notion of the ‘project’, without articulating a constructive proposal. Projectivity does not seem to provide an answer; its claim of performativity lacks the program to regain its organising power over contributions from other specialised disciplines and practices. Theory should focus on the terms of our discipline, which are so close to our ‘core beliefs’ regarding architecture that we usually take their meaning for granted. It would be wrong to see this focus of theory as a withdrawal into the realm of language. Indeed, after a period of theory alienating architects and the general public, it could now create a rhetoric to influence our understanding of our environment, which is itself organised on the level of language. The requirement that theory should
Justin W Walley
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.
Zhu Hong Chen
Full Text Available Chromatin organization and dynamics are integral to global gene transcription. Histone modification influences chromatin status and gene expression. PTEN plays multiple roles in tumor suppression, development, and metabolism. Here, we report on the interplay of PTEN, histone H1, and chromatin. We show that loss of PTEN leads to dissociation of histone H1 from chromatin and decondensation of chromatin. PTEN deletion also results in elevation of histone H4 acetylation at lysine 16, an epigenetic marker for chromatin activation. We found that PTEN and histone H1 physically interact through their C-terminal domains. Disruption of the PTEN C terminus promotes the chromatin association of MOF acetyltransferase and induces H4K16 acetylation. Hyperacetylation of H4K16 impairs the association of PTEN with histone H1, which constitutes regulatory feedback that may reduce chromatin stability. Our results demonstrate that PTEN controls chromatin condensation, thus influencing gene expression. We propose that PTEN regulates global gene transcription profiling through histones and chromatin remodeling.
Nicole I. Bieberstein
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.
Mohammadi-Bardbori, Afshin; Akbarizadeh, Amin Reza; Delju, Fatemeh; Rannug, Agneta
The aim of this study was to gain more information about the mechanisms that regulate expression of the aryl hydrocarbon receptor (AHR) target gene CYP1A1. Human hepatoma cells (HepG2 and Huh7) and human immortalized keratinocytes (HaCaT) were treated with different concentrations of the dietary polyphenolic compound curcumin (CUR) alone or in combination with the natural AHR agonist 6-formylindolo[3,2-b]carbazole (FICZ). In an earlier study, we described that CUR can activate the AHR indirectly by inhibiting metabolic clearance of FICZ. Here, we measured cell viability, activation of AHR signaling, oxidative stress and histone modifying activities in response to CUR at concentrations ranging from 0.1 to 50 μM. We observed apparent non-linear responses on cell viability and activation of AHR signaling. The CYP1A1 expression and the CYP1A1 enzyme activity in the presence of CUR reflected the histone acetylation efficiency observed in nuclear extracts. At the lowest concentration, CUR significantly decreased histone deacetylase activity and increased the FICZ-induced CYP1A1 activity. In contrast, at the highest concentration, CUR increased the formation of reactive oxygen species, significantly inhibited histone acetylation, and temporally decreased FICZ-induced CYP1A1 activity. The results suggest that CUR can both increase and decrease the accessibility of DNA and thereby influence transcriptional responses to the ligand-activated AHR. This suggestion was supported by the fact that chromatin remodeling treatments with trichostatin A, p300, or 5-aza-dC increased CYP1A1 transcription. We conclude that the AHR-dependent transcriptional efficiency is modified by factors that influence the cellular redox status and the chromatin structure. PMID:27041069
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.
An information system architecture defines the components of a system and the interfaces among the components. A good architecture is essential for creating an Integrated Advanced Information Management System (IAIMS) that works as an integrated whole yet is flexible enough to accommodate many users and roles, multiple applications, changing vendors, evolving user needs, and advancing technology. Modularity and layering promote flexibility by reducing the complexity of a system and by restricting the ways in which components may interact. Enterprise-wide mediation promotes integration by providing message routing, support for standards, dictionary-based code translation, a centralized conceptual data schema, business rule implementation, and consistent access to databases. Several IAIMS sites have adopted a client-server architecture, and some have adopted a three-tiered approach, separating user interface functions, application logic, and repositories. PMID:9067884
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 and...
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...... identifies new rationales related to this development, and it argues that “cultural planning” has increasingly shifted its focus from a cultural institutional approach to a more market-oriented strategy that integrates art and business. The role of architecture has changed, too. It not only provides 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 and...
Tvedebrink, Tenna Doktor Olsen
initiatives in Aalborg Hospital to overcome patient undernutrition by refurbishing eating environments, this thesis engages in an investigation of the interior architectural qualities of patient eating environments. The relevance for this holistic perspective, synthesizing health, food and architecture...... 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...... such as a literature review, timeline and historical outline to create a “knowledge map”, which in an eclectic manner merges the positive, normative and polemical knowledge rooted in research, objects and writings. The results of these investigations show that sparse researchbased knowledge exist directly taking...
Felisbino, Marina Barreto; Alves da Costa, Thiago; Gatti, Maria Silvia Viccari; Mello, Maria Luiza Silveira
Diabetes is a complex multifactorial disorder characterized by chronic hyperglycemia due to impaired insulin secretion. Recent observations suggest that the complexity of the disease cannot be entirely accounted for genetic predisposition and a compelling argument for an epigenetic component is rapidly emerging. The use of histone deacetylase inhibitor (HDACi) in clinical setting is an emerging area of investigation. In this study, we have aimed to understand and compare the response of hepatocyte chromatin to valproic acid (VPA) and trichostatin A (TSA) treatments under normoglycemic or hyperglycemic conditions to expand our knowledge about the consequences of HDACi treatment in a diabetes cell model. Under normoglycemic conditions, these treatments promoted chromatin remodeling, as assessed by image analysis and H3K9ac and H3K9me2 abundance. Simultaneously, H3K9ac marks shifted to the nuclear periphery accompanied by HP1 dissociation from the heterochromatin and a G1 cell cycle arrest. More striking changes in the cell cycle progression and mitotic ratios required drastic treatment. Under hyperglycemic conditions, high glucose per se promoted chromatin changes similar to those promoted by VPA and TSA. Nonetheless, these results were not intensified in cells treated with HDACis under hyperglycemic conditions. Despite the absence of morphological changes being promoted, HDACi treatment seems to confer a physiological meaning, ameliorating the cellular hyperglycemic state through reduction of glucose production. These observations allow us to conclude that the glucose level to which the hepatocytes are subjected affects how chromatin responds to HDACi and their action under high-glucose environment might not reflect on chromatin remodeling. J. Cell. Physiol. 231: 2257-2265, 2016. © 2016 Wiley Periodicals, Inc. PMID:26888775
This study was conducted to evaluate the distribution of X-chromatin among Jordanian women at different age groups. Results will be compared with other studies for possible racial and environmental effects on X-chromatin distribution. Blood samples were drawn from all women subjected to this study by finger prick and stained with Wright's stain. X-chromatin positive polymorphonuclear cells were counted and corrected for percentage. Samples were taken during the late 2002 and early 2003 from healthy women attending routine checkup in health centers in Northern Jordan. The number of X-chromatin was highest in the 50 and above years age group. The number of X-chromatin was 14-18% in other age groups. These results were in accordance with other studies. It seems that racial and environmental factors are ineffective on distribution of X-chromatin in Jordanian women. These data could be used as as reference for further studies. (author)
and other spaces that architects are preoccupied with. On the other hand, the distinction between architecture and design is not merely one of scale. Design and architecture represent – at least in Denmark – also quite different disciplinary traditions and methods. Where designers develop prototypes......, architects tend to work with models and plans that are not easily understood by lay people. Further, many architects are themselves sceptical towards notions of user-involvement and collaborative design. They fear that the imagination of citizens and users is restricted to what they are already familiar with...
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....
Multithreaded architectures now appear across the entire range of computing devices, from the highest-performing general purpose devices to low-end embedded processors. Multithreading enables a processor core to more effectively utilize its computational resources, as a stall in one thread need not cause execution resources to be idle. This enables the computer architect to maximize performance within area constraints, power constraints, or energy constraints. However, the architectural options for the processor designer or architect looking to implement multithreading are quite extensive and
Daniel P. Caley
Full Text Available The way in which the genome of a multicellular organism can orchestrate the differentiation of trillions of cells and many organs, all from a single fertilized egg, is the subject of intense study. Different cell types can be defined by the networks of genes they express. This differential expression is regulated at the epigenetic level by chromatin modifications, such as DNA and histone methylation, which interact with structural and enzymatic proteins, resulting in the activation or silencing of any given gene. While detailed mechanisms are emerging on the role of different chromatin modifications and how these functions are effected at the molecular level, it is still unclear how their deposition across the epigenomic landscape is regulated in different cells. A raft of recent evidence is accumulating that implicates long noncoding RNAs (lncRNAs in these processes. Most genomes studied to date undergo widespread transcription, the majority of which is not translated into proteins. In this review, we will describe recent work suggesting that lncRNAs are more than transcriptional "noise", but instead play a functional role by acting as tethers and guides to bind proteins responsible for modifying chromatin and mediating their deposition at specific genomic locations. We suggest that lncRNAs are at the heart of developmental regulation, determining the epigenetic status and transcriptional network in any given cell type, and that they provide a means to integrate external differentiation cues with dynamic nuclear responses through the regulation of a metastable epigenome. Better characterization of the lncRNA-protein "interactome" may eventually lead to a new molecular toolkit, allowing researchers and clinicians to modulate the genome at the epigenetic level to treat conditions such as cancer.
Arifulin E. A.
Aim. The ultrastructural aspect of replicating chromatin organization is a matter of dispute. Here, we have analyzed the ultrastructural organization of replication foci using prematurely condensed chromosomes (PCC). Methods. To investigate the ultrastructure of replicating chromatin, we have used correlative light and electron microscopy as well as immunogold staining. Results. Replication in PCC occurs in the gaps between condensed chromatin domains. Using correlative light and electron mic...
Cieślik, Marcin; Bekiranov, Stefan
Background Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) is the most widely used method for characterizing the epigenetic states of chromatin on a genomic scale. With the recent availability of large genome-wide data sets, often comprising several epigenetic marks, novel approaches are required to explore functionally relevant interactions between histone modifications. Computational discovery of "chromatin states" defined by such combinatorial interactions enabled desc...
Wang Hongda; Dalal Yamini; Henikoff Steven; Lindsay Stuart
Abstract Background Direct visualization of chromatin has the potential to provide important insights into epigenetic processes. In particular, atomic force microscopy (AFM) can visualize single nucleosomes under physiological ionic conditions. However, AFM has mostly been applied to chromatin that has been reconstituted in vitro, and its potential as a tool for the dissection of native nucleosomes has not been explored. Recently we applied AFM to native Drosophila chromatin containing the ce...
Bai, H; Konat, G W
Although a large body of evidence supports a causative link between oxidative stress and neurodegeneration, the mechanisms are still elusive. We have recently demonstrated that hydrogen peroxide (H(2)O(2)), the major mediator of oxidative stress triggers higher order chromatin degradation (HOCD), i.e. excision of chromatin loops at the matrix attachment regions (MARs). The present study was designed to determine the specificity of H(2)O(2) in respect to HOCD induction. Rat glioma C6 cells were exposed to H(2)O(2) and other oxidants, and the fragmentation of genomic DNA was assessed by field inversion gel electrophoresis (FIGE). S1 digestion before FIGE was used to detect single strand fragmentation. The exposure of C6 cells to H(2)O(2) induced a rapid and extensive HOCD. Thus, within 30 min, total chromatin was single strandedly digested into 50 kb fragments. Evident HOCD was elicited by H(2)O(2) at concentrations as low as 5 micro M. HOCD was mostly reversible during 4-8h following the removal of H(2)O(2) from the medium indicating an efficient relegation of the chromatin fragments. No HOCD was induced by H(2)O(2) in isolated nuclei indicating that HOCD-endonuclease is activated indirectly by cytoplasmic signal pathways triggered by H(2)O(2). The exposure of cells to a synthetic peroxide, i.e. tert-butyrylhydroperoxide (tBH) also induced HOCD, but to a lesser extent than H(2)O(2). Contrary to the peroxides, the exposure of cells to equitoxic concentration of hypochlorite and spermine NONOate, a nitric oxide generator, failed to induce rapid HOCD. These results indicate that rapid HOCD is not a result of oxidative stress per se, but is rather triggered by signaling cascades initiated specifically by H(2)O(2). Furthermore, the rapid and extensive HOCD was observed in several rat and human cell lines challenged with H(2)O(2), indicating that the process is not restricted to glial cells, but rather represents a general response of cells to H(2)O(2). PMID:12421592
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...... 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...... of green architecture. The paper argues that this greenification of facades is insufficient. The green is only a skin cladding the exterior envelope without having a spatial significance. Through the paper it is proposed to flip the order of words from green architecture to architectural green...
The main religions of ancient China were Buddhism，Taoism and Islam, of which Buddhism was the most widespread. As a result, Buddhist temples and towers are found all over China, and have become important components of the country's ancient architecture.
Farrell, Thomas S. C.
Thomas Farrell's "Reflective Teaching" outlines four principles that take teachers from just doing reflection to making it a way of being. Using the four principles, Reflective Practice Is Evidence Based, Reflective Practice Involves Dialogue, Reflective Practice Links Beliefs and Practices, and Reflective Practice Is a Way of Life,…
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...... discusses the perspectives of using interactive technologies for performative objects, which are able to register the impulses of urban activity and reproduce the contexts of the city. In this way the performative environment is established as an event setting providing an embodied experience as a ‘quasi......-object' that can couple relationships between architecture, humans and society. These performative relationships between digital and physical environments are seen as illustrative of the social production of space by performance and the creative production of identity. The paper reflects on the perspectives of...
Sheval, E V; Prusov, A N; Kireev, I I; Fais, D; Polyakov, V Yu
The method of chromatin photo-stabilization by the action of visible light in the presence of ethidium bromide was used for investigation of higher-level chromatin structures in isolated nuclei. As a model we used rat hepatocyte nuclei isolated in buffers which stabilized or destabilized nuclear matrix. Several higher-level chromatin structures were visualized: 100nm globules-chromomeres, chains of chromomeres-chromonemata, aggregates of chromomeres-blocks of condensed chromatin. All these structures were completely destroyed by 2M NaCl extraction independent of the matrix state, and DNA was extruded from the residual nuclei (nuclear matrices) into a halo. These results show that nuclear matrix proteins do not play the main role in the maintenance of higher-level chromatin structures. Preliminary irradiation led to the reduction of the halo width in the dose-dependent manner. In regions of condensed chromatin of irradiated nucleoids there were discrete complexes consisting of DNA fibers radiating from an electron-dense core and resembling the decondensed chromomeres or the rosette-like structures. As shown by the analysis of proteins bound to irradiated nuclei upon high-salt extraction, irradiation presumably stabilized the non-histone proteins. These results suggest that in interphase nuclei loop domains are folded into discrete higher-level chromatin complexes (chromomeres). These complexes are possibly maintained by putative non-histone proteins, which are extracted with high-salt buffers from non-irradiated nuclei. PMID:12127937
Tsai, Yu-Cheng; Cooke, Nancy E; Liebhaber, Stephen A
The relationships of higher order chromatin organization to mammalian gene expression remain incompletely defined. The human Growth Hormone (hGH) multigene cluster contains five gene paralogs. These genes are selectively activated in either the pituitary or the placenta by distinct components of a remote locus control region (LCR). Prior studies have revealed that appropriate activation of the placental genes is dependent not only on the actions of the LCR, but also on the multigene composition of the cluster itself. Here, we demonstrate that the hGH LCR 'loops' over a distance of 28 kb in primary placental nuclei to make specific contacts with the promoters of the two GH genes in the cluster. This long-range interaction sequesters the GH genes from the three hCS genes which co-assemble into a tightly packed 'hCS chromatin hub'. Elimination of the long-range looping, via specific deletion of the placental LCR components, triggers a dramatic disruption of the hCS chromatin hub. These data reveal a higher-order structural pathway by which long-range looping from an LCR impacts on local chromatin architecture that is linked to tissue-specific gene regulation within a multigene cluster. PMID:26893355
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.
Svenningsen Kajita, Heidi
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...
Daniel, Jeremy A; Nussenzweig, André
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...
Grøntved, Lars; Bandle, Russell; John, Sam;
BACKGROUND: The challenge in extracting genome-wide chromatin features from limiting clinical samples poses a significant hurdle in identification of regulatory marks that impact the physiological or pathological state. Current methods that identify nuclease accessible chromatin are reliant on la...
Mahmoud, K Gh M; El-Sokary, A A E; Abdel-Ghaffar, A E; Abou El-Roos, M E A; Ahmed, Y F
This study was conducted to determine chromatin integrity and DNA damage by DNA electrophoresis and comet assays of buffalo fresh and frozen semen. Semen samples were collected from four buffalo bulls and evaluated after freezing for semen motility, viability, sperm abnormalities, chromatin integrity and DNA damage. A significant variation was found in semen parameters after thawing. Highly significant differences (Partificial insemination. PMID:27175169
Rennoll-Bankert, Kristen E.; Dumler, J. Stephen
Bacterial pathogens can alter global host gene expression via histone modifications and chromatin remodeling in order to subvert host responses, including those involved with innate immunity, allowing for bacterial survival. Shigella flexneri, Listeria monocytogenes, Chlamydia trachomatis, and Anaplasma phagocytophilum express effector proteins that modify host histones and chromatin structure. A. phagocytophilum modulates granulocyte respiratory burst in part by dampening transcription of se...
Hendriks, Ivo A; Treffers, Louise W; Verlaan-de Vries, Matty; Olsen, Jesper V; Vertegaal, Alfred C O
identified 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...
Meshorer, Eran; Herrmann, Harald; Raška, Ivan
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.
Pudji Pratitis Wismantara
Full Text Available There are two points of departure in the design of mosque architecture in Nusantara, namely architectural homogeneity and architectural hybridity. Each provides the legitimacy of the architecture of identity formation. This paper seeks to explore the comparative, the concept of homogeneity and hybridity architecture, with a critical theory approach. The results of this search is, the concept of architectural homogeneity establishing assumption that certain architectural forms are supposed to represent "universal identity and modernity" of Muslim architecture. Meanwhile, the concept of architectural hybridity to show enrichment architecture identity because of the attempt to combine aspects of the universality of Islam with locality of Nusantara. Both these aspects can be positioned as the two subjects of mutual dialogue in a parallel position. As architecture strategy, the concept of hybridity reflects the effort or ijtihad in interpreting local and universal contextuality in the contemporary conditions that are constantly evolving and open.Keywords: Nusantara mosque, hybridity of architecture, homogeneity of architecture, architecture strategy
Green, G R
Histone variants illuminate the behavior of chromatin through their unique structures and patterns of postsynthetic modification. This review examines the literature on heteromorphous histone structures in chromatin, structures that are primary targets for histone kinases and phosphatases in vivo. Special attention is paid to certain well-studied experimental systems: mammalian culture cells, chicken erythrocytes, sea urchin sperm, wheat sprouts, Tetrahymena, and budding yeast. A common theme emerges from these studies. Specialized, highly basic structures in histone variants promote chromatin condensation in a variety of developmental situations. Before, and sometimes after condensed chromatin is formed, the chromatin is rendered soluble by phosphorylation of the heteromorphous regions, preventing their interaction with linker DNA. A simple structural model accounting for histone variation and phosphorylation is presented. PMID:11467741
Völker-Albert, Moritz Carl; Pusch, Miriam Caroline; Schmidt, Andreas; Imhof, Axel
Here, we use LC-MS/MS and SWATH-MS to describe the kinetics of in vitro assembled chromatin supported by an embryo extract prepared from preblastoderm Drosophila melanogaster embryos (DREX). This system allows easy manipulation of distinct aspects of chromatin assembly such as post-translational histone modifications, the levels of histone chaperones and the concentration of distinct DNA binding factors. In total, 480 proteins have been quantified as chromatin enriched factors and their binding kinetics have been monitored in the time course of 15 min, 1 h and 4 h of chromatin assembly. The data accompanying the manuscript on this approach, Völker-Albert et al., 2016 "A quantitative proteomic analysis of in vitro assembled chromatin" , has been deposited to the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository with the dataset identifier submission number PRIDE: PXD002537 and PRIDE: PXD003445. PMID:27331114
Hypersensitive domains are the most prominent features of transcriptionally active chromatin. In the case of the β/sup A/-globin gene, it seems likely that two or more protein factors are capable of binding to the DNA so tightly that the nucleosome is prevented from binding. We have shown that nucleosomes, once bound in the assembly process in vitro, cannot be displaced. The interaction of the 5S gene transcription factor TFIIIA with its target DNA also is blocked by histones, and it has been suggested that the activation of the gene must occur during replication, before histones are reassembled on the DNA. We suppose that a similar mechanism may govern the binding of the hypersensitivity factors. It should be noted that nucleosomes are excluded not only from the sites to which the factors bind, but also from the regions between the two domains and at either side. 12 refs., 6 figs
Perpelescu, Marinela; Hori, Tetsuya; Toyoda, Atsushi; Misu, Sadahiko; Monma, Norikazu; Ikeo, Kazuho; Obuse, Chikashi; Fujiyama, Asao; Fukagawa, Tatsuo
The CENP-A-specific chaperone HJURP mediates CENP-A deposition at centromeres. The N-terminal region of HJURP is responsible for binding to soluble CENP-A. However, it is unclear whether other regions of HJURP have additional functions for centromere formation and maintenance. In this study, we generated chicken DT40 knockout cell lines and gene replacement constructs for HJURP to assess the additional functions of HJURP in vivo. Our analysis revealed that the middle region of HJURP associates with the Mis18 complex protein M18BP1/KNL2 and that the HJURP-M18BP1 association is required for HJURP function. In addition, on the basis of the analysis of artificial centromeres induced by ectopic HJURP localization, we demonstrate that HJURP exhibits a centromere expansion activity that is separable from its CENP-A-binding activity. We also observed centromere expansion surrounding natural centromeres after HJURP overexpression. We propose that this centromere expansion activity reflects the functional properties of HJURP, which uses this activity to contribute to the plastic establishment of a centromeric chromatin structure. PMID:26063729
Melcer, Shai; Hezroni, Hadas; Rand, Eyal; Nissim-Rafinia, Malka; Skoultchi, Arthur; Stewart, Colin L.; Bustin, Michael; Meshorer, Eran
Embryonic stem cells are characterized by unique epigenetic features including decondensed chromatin and hyperdynamic association of chromatin proteins with chromatin. Here we investigate the potential mechanisms that regulate chromatin plasticity in embryonic stem cells. Using epigenetic drugs and mutant embryonic stem cells lacking various chromatin proteins, we find that histone acetylation, G9a-mediated histone H3 lysine 9 (H3K9) methylation and lamin A expression, all affect chromatin pr...
Leigh, Jennifer S; Bailey, Richard
Although widely employed in professional practice of all kinds, ‘reflection’ and ‘reflective practice’ can be considered ‘success words’. That is, they elicit positive and supportive responses and yet the concepts are vague, ill-defined, contradictory and reflective skills can be hard to teach. Using examples from education and somatic movement therapy, we argue that a purely analytical approach to reflective practice that involves reflecting on thoughts alone is likely to lead into a negativ...
Herssens, Jasmien; Heylighen, Ann
Universal Design is a recent design paradigm which aims at handicap elimination in the physical environment and strives for a more humanized architecture. After pointing out the value of Universal Design, the paper advances human centred design as a possible methodology to make this paradigm operational. Key to this methodology is the explicit attention for cognitive human factors in experiencing space and—the focus of this paper—for the role played by the sense of tou...
Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Po;
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...
Greenslade, Thomas B., Jr.
Discusses and provides an example of reflectivity approximation to determine whether reflection will occur. Provides a method to show thin-film interference on a projection screen. Also applies the reflectivity concepts to electromagnetic wave systems. (MVL)
Hirakawa, Takeshi; Matsunaga, Sachihiro
In plants, chromatin dynamics spatiotemporally change in response to various environmental stimuli. However, little is known about chromatin dynamics in the nuclei of plants. Here, we introduce a three-dimensional, live-cell imaging method that can monitor chromatin dynamics in nuclei via a chromatin tagging system that can visualize specific genomic loci in living plant cells. The chromatin tagging system is based on a bacterial operator/repressor system in which the repressor is fused to fluorescent proteins. A recent refinement of promoters for the system solved the problem of gene silencing and abnormal pairing frequencies between operators. Using this system, we can detect the spatiotemporal dynamics of two homologous loci as two fluorescent signals within a nucleus and monitor the distance between homologous loci. These live-cell imaging methods will provide new insights into genome organization, development processes, and subnuclear responses to environmental stimuli in plants. PMID:27557696
Heimdal, Elisabeth Jacobsen
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...... to create human habitation is not new. As Diether S. Hope phrases it, referring to tents: The history of development of humanity would be barely conceivable without free spanning textile membrane structures....
Vicent, Guillermo P; Nacht, A Silvina; Zaurín, Roser; Ballaré, Cecilia; Clausell, Jaime; Beato, Miguel
Steroid hormones regulate gene expression by interaction of their receptors with hormone-responsive elements on DNA or with other transcription factors, but they can also activate cytoplasmic signaling cascades. Rapid activation of Erk by progestins via an interaction of the progesterone receptor (PR) with the estrogen receptor is critical for transcriptional activation of the mouse mammary tumor virus (MMTV) promoter and other progesterone target genes. Erk activation leads to the phosphorylation of PR, activation of mitogen- and stress-activated protein kinase 1, and the recruitment of a complex of the three activated proteins and of P300/CBP-associated factor (PCAF) to a single nucleosome, resulting in the phosphoacetylation of histone H3 and the displacement of heterochromatin protein 1γ. Hormone-dependent gene expression requires ATP-dependent chromatin remodeling complexes. Two switch/sucrose nonfermentable-like complexes, Brahma-related gene 1-associated factor (BAF) and polybromo-BAF are present in breast cancer cells, but only BAF is recruited to the MMTV promoter and cooperates with PCAF during activation of hormone-responsive promoters. PCAF acetylates histone H3 at K14, an epigenetic mark recognized by BAF subunits, thus anchoring the complex to chromatin. BAF catalyzes localized displacement of histones H2A and H2B, facilitating access of nuclear factor 1 and additional PR complexes to the hidden hormone-responsive elements on the MMTV promoter. The linker histone H1 is a structural component of chromatin generally regarded as a general repressor of transcription. However, it contributes to a better regulation of the MMTV promoter by favoring a more homogeneous nucleosome positioning, thus reducing basal transcription and actually enhancing hormone induced transcription. During transcriptional activation, H1 is phosphorylated and displaced from the promoter. The kinase cyclin-dependent kinase 2 is activated after progesterone treatment and could
We investigated thymine dimer excision from xeroderma pigmentosum (XP) chromatin in the cell-free reconstruction system. The normal-cell extract performed specific dimer excision from native chromatin and DNA isolated from 100 J/m2-irradiated cells. Such an excision in vitro was rapid and required high concentrations of extract. The extracts of XP group A, C and G cells were unable to excise from their own native-chromatin, but capable of excising from chromatin deprived of loosely bound nonhistone proteins with 0.35 M NaCl, as were from purified DNA. Thus, group A, C and G cells are most likely to be defective in the specific XP factors facilitating the excising activity under multicomponent regulation at the chromatin level. Further, either of group A, C and G extracts successfully complemented the native chromatin of the alternative groups. Uniquely, the XP group D extract excised dimers from native chromatin in the normal fashion under the condition. These results suggest that XP group A, C, D and G cells examined may not be defective in the dimer specific endonuclease and exonuclease per se. 19 references, 3 figures, 2 tables
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.
Bahabri, Rihab R.
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.
Full Text Available 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.
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
Handoko, Lusy; Xu, Han; Li, Guoliang; Ngan, Chew Yee; Chew, Elaine; Schnapp, Marie; Lee, Charlie Wah Heng; Ye, Chaopeng; Ping, Joanne Lim Hui; Mulawadi, Fabianus; Wong, Eleanor; Sheng, Jianpeng; Zhang, Yubo; Poh, Thompson; Chan, Chee Seng; Kunarso, Galih; Shahab, Atif; Bourque, Guillaume; Cacheux-Rataboul, Valere; Sung, Wing-Kin; Ruan, Yijun; Wei, Chia-Lin
Mammalian genomes are viewed as functional organizations that orchestrate spatial and temporal gene regulation. CTCF, the most characterized insulator-binding protein, has been implicated as a key genome organizer. Yet, little is known about CTCF-associated higher order chromatin structures at a global scale. Here, we applied Chromatin Interaction Analysis by Paired-End-Tag sequencing to elucidate the CTCF-chromatin interactome in pluripotent cells. From this analysis, 1,480 cis and 336 trans interacting loci were identified with high reproducibility and precision. Associating these chromatin interaction loci with their underlying epigenetic states, promoter activities, enhancer binding and nuclear lamina occupancy, we uncovered five distinct chromatin domains that suggest potential new models of CTCF function in chromatin organization and transcriptional control. Specifically, CTCF interactions demarcate chromatin-nuclear membrane attachments and influence proper gene expression through extensive crosstalk between promoters and regulatory elements. This highly complex nuclear organization offers insights towards the unifying principles governing genome plasticity and function. PMID:21685913
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.
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: email@example.com [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)
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.
Clauvelin, N.; Lo, P.; Kulaeva, O. I.; Nizovtseva, E. V.; Diaz-Montes, J.; Zola, J.; Parashar, M.; Studitsky, V. M.; Olson, W. K.
The dynamic organization of chromatin plays an essential role in the regulation of gene expression and in other fundamental cellular processes. The underlying physical basis of these activities lies in the sequential positioning, chemical composition, and intermolecular interactions of the nucleosomes—the familiar assemblies of ˜150 DNA base pairs and eight histone proteins—found on chromatin fibers. Here we introduce a mesoscale model of short nucleosomal arrays and a computational framework that make it possible to incorporate detailed structural features of DNA and histones in simulations of short chromatin constructs. We explore the effects of nucleosome positioning and the presence or absence of cationic N-terminal histone tails on the ‘local’ inter-nucleosomal interactions and the global deformations of the simulated chains. The correspondence between the predicted and observed effects of nucleosome composition and numbers on the long-range communication between the ends of designed nucleosome arrays lends credence to the model and to the molecular insights gleaned from the simulated structures. We also extract effective nucleosome-nucleosome potentials from the simulations and implement the potentials in a larger-scale computational treatment of regularly repeating chromatin fibers. Our results reveal a remarkable effect of nucleosome spacing on chromatin flexibility, with small changes in DNA linker length significantly altering the interactions of nucleosomes and the dimensions of the fiber as a whole. In addition, we find that these changes in nucleosome positioning influence the statistical properties of long chromatin constructs. That is, simulated chromatin fibers with the same number of nucleosomes exhibit polymeric behaviors ranging from Gaussian to worm-like, depending upon nucleosome spacing. These findings suggest that the physical and mechanical properties of chromatin can span a wide range of behaviors, depending on nucleosome
Haberle, Vanja; Lenhard, Boris
Core promoters are minimal regions sufficient to direct accurate initiation of transcription and are crucial for regulation of gene expression. They are highly diverse in terms of associated core promoter motifs, underlying sequence composition and patterns of transcription initiation. Distinctive features of promoters are also seen at the chromatin level, including nucleosome positioning patterns and presence of specific histone modifications. Recent advances in identifying and characterizing promoters using next-generation sequencing-based technologies have provided the basis for their classification into functional groups and have shed light on their modes of regulation, with important implications for transcriptional regulation in development. This review discusses the methodology and the results of genome-wide studies that provided insight into the diversity of RNA polymerase II promoter architectures in vertebrates and other Metazoa, and the association of these architectures with distinct modes of regulation in embryonic development and differentiation. PMID:26783721
Borochov, N; Ausio, J; Eisenberg, H
We have investigated the interaction of divalent ions with chromatin towards a closer understanding of the role of metal ions in the cell nucleus. The first row transition metal ion chlorides MnCl2, CoCl2, NiCl2 and CuCl2 lead to precipitation of chicken erythrocyte chromatin at a significantly lower concentration than the alkali earth metal chlorides MgCl2, CaCl2 and BaCl2. A similar distinction can be made for the compaction of chromatin to the "30 nm" solenoid higher order structure which ...
Mukhopadhyay, Rituparna; Yu, Wenqiang; Whitehead, Joanne; Xu, Junwang; Lezcano, Magda; Pack, Svetlana; Kanduri, Chandrasekhar; Kanduri, Meena; Ginjala, Vasudeva; Vostrov, Alexander; Quitschke, Wolfgang; Chernukhin, Igor; Klenova, Elena; Lobanenkov, Victor; Ohlsson, Rolf
All known vertebrate chromatin insulators interact with the highly conserved, multivalent 11-zinc finger nuclear factor CTCF to demarcate expression domains by blocking enhancer or silencer signals in a position-dependent manner. Recent observations document that the properties of CTCF include reading and propagating the epigenetic state of the differentially methylated H19 imprinting control region. To assess whether these findings may reflect a universal role for CTCF targets, we identified...
介绍了建筑反射隔热涂料在工程应用中的主要技术问题和实施要点，包括建筑反射隔热涂料的应用特点、应用方式、涂层构造和技术指标要求，以及设计要点和施工技术等。其主要应用方式是建筑反射隔热涂料一无机保温砂浆外墙外保温体系，以及建筑反射隔热涂料一保温腻子层体系两种方式。设计中，首先应满足建筑节能规定的建筑物传热阻值，并将涂料等效热阻考虑到设计中；涂膜最小厚度和变形缝的设置等也是设计中应当考虑的问题。%The main technical insulation coatings in the enginee problem and implementation points of the architectural reflective thermal ring application were introduced. These contents were included： the application characteristics, the application way, the coating structure, the technical index requests, and the main pionts for design and the construction technology etc. The main application way were the architectural reflective thermal insulating coatings-inorganic thermal insulation mortar system, and the architectural reflective thermal insulating coatings-thermal insulation p energy-saving design was satisfie system. d, and In the the eq thickness of the film and setting deformation design, the thermal resistance of the building regulated in build uivalent thermal resistance of coatings was calculated. The least int were also considered in the design.
In higher eukaryotes, the absence of specific sequence motifs marking the origins of replication has been a serious hindrance to the understanding of the mechanisms that regulate the initiation and the maintenance of the replication program in different cell types. In silico analysis of nucleotide compositional skew has predicted the existence, in the germline, of replication N-domains bordered by putative replication origins and where the skew decreases rather linearly as the signature of a progressive inversion of the average fork polarity. Here, from the demonstration that the average fork polarity can be directly extracted from the derivative of replication timing profiles, we develop a wavelet-based pattern recognition methodology to delineate replication U-domains where the replication timing profile is shaped as a U and its derivative as a N. Replication U-domains are robustly found in seven cell lines as covering a significant portion (40-50%) of the human genome where the replication timing data actually displays some plasticity between cell lines. The early replication initiation zones at U-domains borders are found to be hypersensitive to DNase I cleavage, to be associated with transcriptional activity and to present a significant enrichment in insular-binding proteins CTCF, the hallmark of an open chromatin structure. A comparative analysis of genome-wide chromatin interaction (HiC) data shows that replication-U domains correspond to self-interacting structural high order chromatin units of megabase characteristic size. Taken together, these findings provide evidence that the epigenetic compartmentalization of the human genome into autonomous replication U-domains comes along with an extensive remodelling of the threedimensional chromosome architecture during development or in specific diseases. The observed cell specific conservation of the replication timing between the human and mouse genomes strongly suggests that this chromosome organization into
Costes, Sylvain V; Chiolo, Irene; Pluth, Janice M.; Barcellos-Hoff, Mary Helen; Jakob, Burkhard
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.
B. V. Gurudatta; L. S. Shashidhara; Veena K. Parnaik
Drosophila lamin C (LamC) is a developmentally regulated component of the nuclear lamina. The lamC gene is situated in the fifth intron of the essential gene tout velu (ttv). We carried out genetic analysis of lamC during development. Phenotypic analyses of RNAi-mediated downregulation of lamC expression as well as targeted misexpression of lamin C suggest a role for lamC in cell survival. Of particular interest in the context of laminopathies is the caspase-dependent apoptosis induced by the overexpression of lamin C. Interestingly, misexpression of lamin C in the central nervous system, where it is not normally expressed, did not affect organization of the nuclear lamina. lamC mutant alleles suppressed position effect variegation normally displayed at near-centromeric and telomeric regions. Further, both downregulation and misexpression of lamin C affected the distribution of heterochromatin protein 1. Our results suggest that Drosophila lamC has a tissue-specific role during development and is required for chromatin organization.
Lermontova, Inna; Sandmann, Michael; Mascher, Martin; Schmit, Anne-Catherine; Chabouté, Marie-Edith
Centromeres are chromatin structures that are required for proper separation of chromosomes during mitosis and meiosis. The centromere is composed of centromeric DNA, often enriched in satellite repeats, and kinetochore complex proteins. To date, over 100 kinetochore components have been identified in various eukaryotes. Kinetochore assembly begins with incorporation of centromeric histone H3 variant CENH3 into centromeric nucleosomes. Protein components of the kinetochore are either present at centromeres throughout the cell cycle or localize to centromeres transiently, prior to attachment of microtubules to each kinetochore in prometaphase of mitotic cells. This is the case for the spindle assembly checkpoint (SAC) proteins in animal cells. The SAC complex ensures equal separation of chromosomes between daughter nuclei by preventing anaphase onset before metaphase is complete, i.e. the sister kinetochores of all chromosomes are attached to spindle fibers from opposite poles. In this review, we focus on the organization of centromeric DNA and the kinetochore assembly in plants. We summarize recent advances regarding loading of CENH3 into the centromere, and the subcellular localization and protein-protein interactions of Arabidopsis thaliana proteins involved in kinetochore assembly and function. We describe the transcriptional activity of corresponding genes based on in silico analysis of their promoters and cell cycle-dependent expression. Additionally, barley homologs of all selected A. thaliana proteins have been identified in silico, and their sequences and domain structures are presented. PMID:25976696
Crosslinking induced by ultraviolet light irradiation at 254 nm has been utilized to investigate the structure of chromatin and isolated nucleosomes. The results presented here imply that the four core histones, as well as histone H1, have reactive groups within a bond length of the DNA bases. In nucleosomes depleted of H1, all of the core histones react similarly with the DNA and form crosslinks. In chromatin, the rate of crosslinking of all histones to DNA is essentially similar. Comparison of mononucleosomes, dinucleosomes and whole chromatin shows that the rate of crosslinking increase significantly with increasing number of connected nucleosomes. These differences in the rate of crosslinking are interpreted in terms of interactions between neighbouring nucleosomes on the chromatin fiber, which are absent in an isolated mononucleosome. (orig.)
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.
Bandaria, Jigar N; Qin, Peiwu; Berk, Veysel; Chu, Steven; Yildiz, Ahmet
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, but 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 accumulate DDR signals and become more accessible to telomere-associated proteins. 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
Graziano, V.; Gerchman, S.E.; Schneider, D.K.; Ramakrishnan, V. [Brookhaven National Laboratory, Upton, NY (United States)
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.
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.
Gopalkrishnan, K; Padwal, V; Balaiah, D
A retrospective study was undertaken to investigate whether viscosity alters sperm chromatin integrity. Semen samples were obtained from 269 men attending the infertility clinic. The viscosity was measured quantitatively by needle and syringe method and the viscosity ratio was calculated against distilled water. The chromatin integrity was evaluated by in vitro decondensation test using 1% SDS and 6 mM EDTA. According to the viscosity ratios the samples were divided into 2 groups: I, normal (ratio 9, n = 30) viscosity. Chromatin integrity was significantly lower in the group with higher viscosity. Significant decrease in sperm count and motility were seen in group II as compared to group I. Thus, hyperviscosity of seminal fluid alters the sperm chromatin integrity. PMID:11028927
Gay, Sophie; Foiani, Marco
More than as an inert separation between the inside and outside of the nucleus, the nuclear envelope (NE) constitutes an active toll, which controls the import and export of molecules, and also a hub for a diversity of genomic processes, such as transcription, DNA repair, and chromatin dynamics. Proteins localized at the inner surface of the NE (such as lamins, nuclear pore proteins, lamin-associated proteins) interact with chromatin in a dynamic manner, contributing to the establishment of topological domains. In this review, we address the complex interplay between chromatin and NE. We discuss the divergence of this cross talk during evolution and comment both on the current established models and the most recent findings. In particular, we focus our attention on how the NE cooperates with chromatin in protecting the genome integrity. PMID:26008788
Suter, B.; Livingstone-Zatchej, M; Thoma, F
Yeast and many other organisms use nucleotide excision repair (NER) and photolyase in the presence of light (photoreactivation) to repair cyclobutane pyrimidine dimers (CPDs), a major class of DNA lesions generated by UV light. To study the role of photoreactivation at the chromatin level in vivo, we used yeast strains which contained minichromosomes (YRpTRURAP, YRpCS1) with well-characterized chromatin structures. The strains were either proficient (RAD1) or deficient (rad1 delta) in NER. In...
Hoffman, Michael M; Buske, Orion J; Wang, Jie; Weng, Zhiping; Bilmes, Jeff A; Noble, William Stafford
We trained Segway, a dynamic Bayesian network method, simultaneously on chromatin data from multiple experiments, including positions of histone modifications, transcription-factor binding and open chromatin, all derived from a human chronic myeloid leukemia cell line. In an unsupervised fashion, we identified patterns associated with transcription start sites, gene ends, enhancers, transcriptional regulator CTCF-binding regions and repressed regions. Software and genome browser tracks are at http://noble.gs.washington.edu/proj/segway/. PMID:22426492
Fudenberg, Geoffrey; Mirny, Leonid A.
Recent advances in microscopy and genomic techniques have provided new insight into spatial chromatin organization inside of the nucleus. In particular, chromosome conformation capture data has highlighted the relevance of polymer physics for high-order chromatin organization. In this context, we review basic polymer states, discuss how an appropriate polymer model can be determined from experimental data, and examine the success and limitations of various polymer models of high-order interph...
Barbi, Maria; Mozziconacci, Julien; Victor, Jean-Marc
In the nuclei of eukaryotic cells, DNA is packaged through several levels of compaction in an orderly retrievable way that enables the correct regulation of gene expression. The functional dynamics of this assembly involves the unwinding of the so-called 30 nm chromatin fiber and accordingly imposes strong topological constraints. We present a general method for computing both the twist and the writhe of any winding pattern. An explicit derivation is implemented for the chromatin fiber which ...