Genome-wide mapping of chromatin state of mouse forelimbs

Although the nonrandom nature of interphase chromosome arrangement is widely accepted, how nuclear organization relates to genomic function remains unclear. Nuclear subcompartments may play a role by offering rich microenvironments that regulate chromatin state and ensure optimal transcriptional efficiency. Technological advances now provide genome-wide and four-dimensional analyses, permitting global characterizations of nuclear order. These approaches will help uncover how seemingly separate nuclear processes may be coupled and aid in the effort to understand the role of nuclear organization in development and disease.

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Pluripotency-related, Valproic Acid (VPA)-induced Genome-wide Histone H3 Lysine 9 (H3K9) Acetylation Patterns in Embryonic Stem Cells

Journal of Biological Chemistry ◽

10.1074/jbc.m111.266254 ◽

2011 ◽

Vol 286 (41) ◽

pp. 35977-35988 ◽

Cited By ~ 55

Author(s):

Hadas Hezroni ◽

Badi Sri Sailaja ◽

Eran Meshorer

Keyword(s):

Gene Expression ◽

Valproic Acid ◽

Transcription Factors ◽

Hdac Inhibitor ◽

Embryonic Stem ◽

Chromatin State ◽

Gene Promoters ◽

Histone Marks ◽

Low Level ◽

Genome Wide

Embryonic stem cell (ESC) chromatin is characterized by a unique set of histone modifications, including enrichment for H3 lysine 9 acetylation (H3K9ac). Recent studies suggest that histone deacetylase (HDAC) inhibitors promote pluripotency. Here, using H3K9ac ChIP followed by high throughput sequencing analyses and gene expression in E14 mouse ESCs before and after treatment with a low level of the HDAC inhibitor valproic acid, we show that H3K9ac is enriched at gene promoters and is highly correlated with gene expression and with various genomic features, including different active histone marks and pluripotency-related transcription factors. Curiously, it predicts the cellular location of gene products. Treatment of ESCs with valproic acid leads to a pervasive genome-wide and time-dependent increase in H3K9ac, but this increase is selectively suppressed after 4 h in H3K4me3/H3K27me3 bivalent genes. H3K9ac increase is dependent on the promoter's chromatin state and is affected by the binding of P300, various transcription factors, and active histone marks. This study provides insights into the genomic response of ESCs to a low level of HDAC inhibitor, which leads to increased pluripotency. The results suggest that a mild (averaging less than 40%) but global change in the chromatin state is involved in increased pluripotency and that specific mechanisms operate selectively in bivalent genes to maintain constant H3K9ac levels. Our data support the notion that H3K9ac has an important role in ESC biology.

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Genome-wide Chromatin State Transitions Associated with Developmental and Environmental Cues

Cell ◽

10.1016/j.cell.2012.12.033 ◽

2013 ◽

Vol 152 (3) ◽

pp. 642-654 ◽

Cited By ~ 366

Author(s):

Jiang Zhu ◽

Mazhar Adli ◽

James Y. Zou ◽

Griet Verstappen ◽

Michael Coyne ◽

...

Keyword(s):

Chromatin State ◽

State Transitions ◽

Environmental Cues ◽

Genome Wide

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Genome-wide Analysis of Histone Methylation Reveals Chromatin State-Based Regulation of Gene Transcription and Function of Memory CD8+ T Cells

Immunity ◽

10.1016/j.immuni.2009.05.006 ◽

2009 ◽

Vol 30 (6) ◽

pp. 912-925 ◽

Cited By ~ 175

Author(s):

Yasuto Araki ◽

Zhibin Wang ◽

Chongzhi Zang ◽

William H. Wood ◽

Dustin Schones ◽

...

Keyword(s):

T Cells ◽

Gene Transcription ◽

Cd8 T Cells ◽

Histone Methylation ◽

Chromatin State ◽

Memory Cd8 T Cells ◽

Genome Wide Analysis ◽

Genome Wide ◽

And Function

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Faculty Opinions recommendation of Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1089729.559251 ◽

2008 ◽

Author(s):

Ian Dunham

Keyword(s):

Chromatin State ◽

Genome Wide

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Genome-wide Chromatin Accessibility is Restricted by ANP32E

10.1101/2020.09.08.288241 ◽

2020 ◽

Author(s):

Kristin E. Murphy ◽

Fanju W. Meng ◽

Claire E. Makowski ◽

Patrick J. Murphy

Keyword(s):

Gene Expression ◽

Nucleosome Positioning ◽

Chromatin Accessibility ◽

Chromatin State ◽

Start Site ◽

Transcription Start ◽

Genome Wide ◽

Expression Potential ◽

Gene Expression Levels ◽

Hierarchical Manner

ABSTRACTGenome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning contribute to the accessibility of DNA, but widespread regulators of chromatin state are largely unknown. Our study investigates how control of genomic H2A.Z localization by ANP32E contributes to chromatin state in mouse fibroblasts. We define H2A.Z as a universal chromatin accessibility factor, and demonstrate that through antagonism of H2A.Z, ANP32E restricts genome-wide DNA access. In the absence of ANP32E, H2A.Z accumulates at promoters in a hierarchical manner. H2A.Z initially localizes downstream of the transcription start site, and if H2A.Z is already present downstream, additional H2A.Z accumulates upstream. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor binding, and increased expression of neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.

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chromstaR: Tracking combinatorial chromatin state dynamics in space and time

10.1101/038612 ◽

2016 ◽

Cited By ~ 11

Author(s):

Aaron Taudt ◽

Minh Anh Nguyen ◽

Matthias Heinig ◽

Frank Johannes ◽

Maria Colomé-Tatché

Keyword(s):

Temporal Dynamics ◽

Cell Types ◽

R Package ◽

Developmental Time ◽

Genomic Region ◽

Chromatin State ◽

Post Translational Modifications ◽

Chromatin States ◽

Genome Wide ◽

Experimental Treatments

AbstractBackgroundPost-translational modifications of histone residue tails are an important component of genome regulation. It is becoming increasingly clear that the combinatorial presence and absence of various modifications define discrete chromatin states which determine the functional properties of a locus. An emerging experimental goal is to track changes in chromatin state maps across different conditions, such as experimental treatments, cell-types or developmental time points.ResultsHere we present chromstaR, an algorithm for the computational inference of combinatorial chromatin state dynamics across an arbitrary number of conditions. ChromstaR uses a multivariate Hidden Markov Model to determine the number of discrete combinatorial chromatin states using multiple ChIP-seq experiments as input and assigns every genomic region to a state based on the presence/absence of each modification in every condition. We demonstrate the advantages of chromstaR in the context of three common experimental data scenarios. First, we study how different histone modifications combine to form combinatorial chromatin states in a single tissue. Second, we infer genome-wide patterns of combinatorial state differences between two cell types or conditions. Finally, we study the dynamics of combinatorial chromatin states during tissue differentiation involving up to six differentiation points. Our findings reveal a striking sparcity in the combinatorial organization and temporal dynamics of chromatin state maps.ConclusionschromstaR is a versatile computational tool that facilitates a deeper biological understanding of chromatin organization and dynamics. The algorithm is implemented as an R-package and freely available from http://bioconductor.org/packages/chromstaR/.

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