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Journal ArticleDOI

Regulation of nucleosome dynamics by histone modifications

01 Mar 2013-Nature Structural & Molecular Biology (Nature Publishing Group)-Vol. 20, Iss: 3, pp 259-266
TL;DR: Property of the major types of histone modification in the context of their associated biological processes are considered to view them in light of the cellular mechanisms that regulate nucleosome dynamics.
Abstract: The properties of nucleosomes can be altered in various ways, including by covalent modification of histones. In this Review, the known properties of key histone modifications and the biological processes to which they are linked are examined to place the modifications in the context of nucleosome dynamics—that is, processes in which nucleosomes are translocated, unwrapped, evicted or replaced.
Citations
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Journal ArticleDOI
TL;DR: In this paper, the authors summarize the signalling and epigenetic mechanisms that regulate type I IFN-induced STAT activation and ISG transcription and translation and conclude that these regulatory mechanisms determine the biological outcomes of type I ILN responses and whether pathogens are cleared effectively or chronic infection or autoimmune disease ensues.
Abstract: Type I interferons (IFNs) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. Canonical type I IFN signalling activates the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway, leading to transcription of IFN-stimulated genes (ISGs). Host, pathogen and environmental factors regulate the responses of cells to this signalling pathway and thus calibrate host defences while limiting tissue damage and preventing autoimmunity. Here, we summarize the signalling and epigenetic mechanisms that regulate type I IFN-induced STAT activation and ISG transcription and translation. These regulatory mechanisms determine the biological outcomes of type I IFN responses and whether pathogens are cleared effectively or chronic infection or autoimmune disease ensues.

2,273 citations

Journal ArticleDOI
TL;DR: Elongation is recognized as a key phase in the regulation of transcription by Pol II, revealing that elongation is a highly complex process.
Abstract: Recent advances in sequencing techniques that measure nascent transcripts and that reveal the positioning of RNA polymerase II (Pol II) have shown that the pausing of Pol II in promoter-proximal regions and its release to initiate a phase of productive elongation are key steps in transcription regulation. Moreover, after the release of Pol II from the promoter-proximal region, elongation rates are highly dynamic throughout the transcription of a gene, and vary on a gene-by-gene basis. Interestingly, Pol II elongation rates affect co-transcriptional processes such as splicing, termination and genome stability. Increasing numbers of factors and regulatory mechanisms have been associated with the steps of transcription elongation by Pol II, revealing that elongation is a highly complex process. Elongation is thus now recognized as a key phase in the regulation of transcription by Pol II.

720 citations

Journal ArticleDOI
TL;DR: In this review, both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory are discussed.
Abstract: Plants frequently have to weather both biotic and abiotic stressors, and have evolved sophisticated adaptation and defense mechanisms. In recent years, chromatin modifications, nucleosome positioning, and DNA methylation have been recognized as important components in these adaptations. Given their potential epigenetic nature, such modifications may provide a mechanistic basis for a stress memory, enabling plants to respond more efficiently to recurring stress or even to prepare their offspring for potential future assaults. In this review, we discuss both the involvement of chromatin in stress responses and the current evidence on somatic, intergenerational, and transgenerational stress memory.

443 citations


Cites background from "Regulation of nucleosome dynamics b..."

  • ...org/publicdomain/ze The structure of chromatin regulates the accessibility of genes for the transcriptional machinery, and is thus an integral part of regulated gene expression in stress responses and development [8, 9]....

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Journal ArticleDOI
TL;DR: Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general Regulatory factors, chromatin remodellers, chaperones and polymerases.
Abstract: Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases. It is now known that these dynamics regulate diverse cellular processes ranging from gene transcription to DNA replication and repair.

361 citations

Journal ArticleDOI
TL;DR: Elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer and could serve as biomarkers and novel therapeutic targets in human diseases.
Abstract: Histones and their post-translational modifications have key roles in chromatin remodeling and gene transcription Besides intranuclear functions, histones act as damage-associated molecular pattern molecules when they are released into the extracellular space Administration of exogenous histones to animals leads to systemic inflammatory and toxic responses through activating Toll-like receptors and inflammasome pathways Anti-histone treatment (eg, neutralizing antibodies, activated protein C, recombinant thrombomodulin, and heparin) protect mice against lethal endotoxemia, sepsis, ischemia/reperfusion injury, trauma, pancreatitis, peritonitis, stroke, coagulation, and thrombosis In addition, elevated serum histone and nucleosome levels have been implicated in multiple pathophysiological processes and progression of diseases including autoimmune diseases, inflammatory diseases, and cancer Therefore, extracellular histones could serve as biomarkers and novel therapeutic targets in human diseases

326 citations

References
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Journal ArticleDOI
23 Feb 2007-Cell
TL;DR: The surface of nucleosomes is studded with a multiplicity of modifications that can dictate the higher-order chromatin structure in which DNA is packaged and can orchestrate the ordered recruitment of enzyme complexes to manipulate DNA.

10,046 citations

Journal ArticleDOI
02 Aug 2007-Nature
TL;DR: The application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells is reported and it is shown that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms.
Abstract: We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences Lysine 4 and lysine 9 trimethylation marks imprinting control regions Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations

4,166 citations

Journal ArticleDOI
01 Mar 2001-Nature
TL;DR: A stepwise model for the formation of a transcriptionally silent heterochromatin is provided: SUV39H1 places a ‘methyl marker’ on histone H3, which is then recognized by HP1 through its chromo domain, which may also explain the stable inheritance of theheterochromatic state.
Abstract: Heterochromatin protein 1 (HP1) is localized at heterochromatin sites where it mediates gene silencing. The chromo domain of HP1 is necessary for both targeting and transcriptional repression. In the fission yeast Schizosaccharomyces pombe, the correct localization of Swi6 (the HP1 equivalent) depends on Clr4, a homologue of the mammalian SUV39H1 histone methylase. Both Clr4 and SUV39H1 methylate specifically lysine 9 of histone H3 (ref. 6). Here we show that HP1 can bind with high affinity to histone H3 methylated at lysine 9 but not at lysine 4. The chromo domain of HP1 is identified as its methyl-lysine-binding domain. A point mutation in the chromo domain, which destroys the gene silencing activity of HP1 in Drosophila, abolishes methyl-lysine-binding activity. Genetic and biochemical analysis in S. pombe shows that the methylase activity of Clr4 is necessary for the correct localization of Swi6 at centromeric heterochromatin and for gene silencing. These results provide a stepwise model for the formation of a transcriptionally silent heterochromatin: SUV39H1 places a 'methyl marker' on histone H3, which is then recognized by HP1 through its chromo domain. This model may also explain the stable inheritance of the heterochromatic state.

2,811 citations

Journal ArticleDOI
05 May 2011-Nature
TL;DR: This study presents a general framework for deciphering cis-regulatory connections and their roles in disease, and maps nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions.
Abstract: Chromatin profiling has emerged as a powerful means of genome annotation and detection of regulatory activity. The approach is especially well suited to the characterization of non-coding portions of the genome, which critically contribute to cellular phenotypes yet remain largely uncharted. Here we map nine chromatin marks across nine cell types to systematically characterize regulatory elements, their cell-type specificities and their functional interactions. Focusing on cell-type-specific patterns of promoters and enhancers, we define multicell activity profiles for chromatin state, gene expression, regulatory motif enrichment and regulator expression. We use correlations between these profiles to link enhancers to putative target genes, and predict the cell-type-specific activators and repressors that modulate them. The resulting annotations and regulatory predictions have implications for the interpretation of genome-wide association studies. Top-scoring disease single nucleotide polymorphisms are frequently positioned within enhancer elements specifically active in relevant cell types, and in some cases affect a motif instance for a predicted regulator, thus suggesting a mechanism for the association. Our study presents a general framework for deciphering cis-regulatory connections and their roles in disease.

2,646 citations

Journal ArticleDOI
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2,378 citations