Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Genome-wide maps of epigenetic features in G1E model and in mouse primary erythroblasts.

ABSTRACT: Interplays among lineage specific nuclear proteins, chromatin modifying enzymes and the basal transcription machinery govern cellular differentiation, but their dynamics of actions and coordination with transcriptional control are not fully understood. Alterations in chromatin structure appear to establish a permissive state for gene activation at some loci but they play an integral role in activation at other loci. To determine the predominant roles of chromatin states and factor occupancy in directing gene regulation during differentiation, we mapped chromatin accessibility, histone modifications, and nuclear factor occupancy genome-wide during mouse erythroid differentiation dependent on the master regulatory transcription factor GATA1. Remarkably, despite extensive changes in gene expression, the chromatin state profiles (proportions of a gene in a chromatin state dominated by activating or repressive histone modifications) and accessibility remain largely unchanged during GATA1-induced erythroid differentiation. In contrast, gene induction and repression are strongly associated with changes in patterns of transcription factor occupancy. Our results indicate that during erythroid differentiation, the broad features of chromatin states are established at the stage of lineage commitment, largely independently of GATA1. These determine permissiveness for expression, with subsequent induction or repression mediated by distinctive combinations of transcription factors. Using ChIP-Seq technology to examine DNase hypersensitivity, three transcription factors, and four histone modifications in Gata1-null murine G1E line and rescued G1E-ER4 subline, and also two of the transcription factors in mouse primary erythroblasts. ChIP input DNA was sequenced in each cell type as controls.

ORGANISM(S): Mus musculus

SUBMITTER: Ross Hardison

PROVIDER: E-GEOD-30142 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration.

Wu Weisheng W Cheng Yong Y Keller Cheryl A CA Ernst Jason J Kumar Swathi Ashok SA Mishra Tejaswini T Morrissey Christapher C Dorman Christine M CM Chen Kuan-Bei KB Drautz Daniela D Giardine Belinda B Shibata Yoichiro Y Song Lingyun L Pimkin Max M Crawford Gregory E GE Furey Terrence S TS Kellis Manolis M Miller Webb W Taylor James J Schuster Stephan C SC Zhang Yu Y Chiaromonte Francesca F Blobel Gerd A GA Weiss Mitchell J MJ Hardison Ross C RC

Genome research 20110727 10

Interplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordination with transcriptional control are not fully understood. Alterations in chromatin structure appear to establish a permissive state for gene activation at some loci, but they play an integral role in activation at other loci. To determine the predominant roles of chromatin states and factor occupancy in ...[more]

PMID: 21795386

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Project description:Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factors dissociate from mitotic chromosomes, the observation that certain nuclear factors and chromatin features remain associated with individual loci during mitosis originated the hypothesis that they could provide transcriptional memory through mitosis. To obtain the first genome-wide view of the dynamics of chromatin structure during mitosis, we compared the DNase sensitivity of interphase and mitotic chromatin at two stages of cellular maturation in a rapidly dividingmurine erythroblastmodel. Despite global chromosome condensation visible during mitosis at the microscopic level, the chromatin accessibility landscape is largely unaltered. However, mitotic chromatin accessibility is locally dynamic, with individual loci maintaining none, some, or all of their interphase accessibility. Mitotic reduction in accessibility occurs primarily within narrow, highly hypersensitive sites that frequently coincide with transcription factor binding sites, whereas broader domains of moderate accessibility tend to be more stable. In mitosis, proximal promoters generally maintain their accessibility, whereas distal regulatory elements preferentially lose accessibility. Promoters with the highest degree of accessibility preservation in mitosis tend to also be accessible across many murine tissues in interphase. Transcription factor GATA1 exerts site-specific changes in interphase accessibility that are most pronounced at distal regulatory elements, but does not visibly influence mitotic accessibility. We conclude that features of open chromatin are remarkably stable through mitosis and are modulated at the level of individual genes and regulatory elements. Dnase-Seq data is integrated with Chip-seq [GSE36589, GSE30142] and RNA-seq to examine epigentic changes in mitosis. We performed DNase-seq on two cell lines, G1E and G1E-ER4, both on an asynchronus population, and on a sample of cells in mitosis; each of the 4 experiments in triplicate.

Dataset Information

Genome-wide maps of epigenetic features in G1E model and in mouse primary erythroblasts.

Publications

Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration.

Similar Datasets

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