PreprintCited by 122Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration

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Wu, Weisheng, Cheng, Yong, Keller, Cheryl A., Ernst, Jason, Kumar, Swathi Ashok, Mishra, Tejaswini, Morrissey, Christapher, Dorman, Christine M. +17 more·2011·Genome Research

Abstract

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 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. Notably, 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.

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  • A difference in GATA1 and SPI1 co-binding between the two types of SPI1-bound enhancers was also seen using GATA1 peaks from G1E-ER4 restored for GATA1 activity or Ter119+ foetal liver proerythroblasts.

    “Such a difference in GATA1 and SPI1 co-binding between the two types of SPI1-bound enhancers was also seen using GATA1 peaks from G1E-ER4 restored for GATA1 activity (64,65) or Ter119+ foetal liver proerythroblasts (66) (Supplementary Figure S9A), revealing a specific enrichment for GATA1 binding sites at SPI1-deacetylated enhancers.”

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Authors
Wu, W., Cheng, Y., Keller, C. A., Ernst, J., Kumar, S. A., Mishra, T., Morrissey, C., Dorman, C. M., Chen, K.-B., Drautz, D., Giardine, B., Shibata, Y., Song, L., Pimkin, M., Crawford, G. E., Furey, T. S., Kellis, M., Miller, W., Taylor, J., Schuster, S. C., Zhang, Y., Chiaromonte, F., Blobel, G. A., Weiss, M. J., & Hardison, R. C.
Affiliations
  • Pennsylvania State University (US)
  • Broad Institute (US)
  • Duke University (US)
  • University of North Carolina at Chapel Hill (US)
  • Emory University (US)
  • Children's Hospital of Philadelphia (US)
Venue
Genome Research
Published
2011-07-27
Volume
21
Issue
10
Pages
1659-1671
ISSN
1088-9051 (ISSN-L)
OpenAlex
W4299645797
Cited by
118
References
63
Citations by year
2025: 1 · 2023: 4 · 2022: 3 · 2021: 8 · 2020: 10 · 2019: 9 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 11 · 2014: 16 · 2013: 11 · 2012: 22
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
  • UNC Libraries
Funders
  • National Science Foundation (0821527, 0905968)
  • Gordon and Betty Moore Foundation
  • Leukemia and Lymphoma Society
  • University of Pennsylvania
  • Pennsylvania State University (OCI-0821527)
  • National Institutes of Health
  • National Human Genome Research Institute (R01HG004718, RC2HG005573, RC1HG005334, RC2HG005639, R01HG004037, R01HG002238)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065806, R01DK058044, R01DK054937)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
erythroid differentiation, GATA-1, chromatin accessibility, histone modifications, transcription factor occupancy, chromatin state, lineage commitment, epigenetic landscape, transcriptional regulation
MeSH terms
T-Cell Acute Lymphocytic Leukemia Protein 1, Animals, Cell Differentiation, Cell Line, Erythropoiesis, Estradiol, Peptide Hydrolases, Protein Binding, Proto-Oncogene Proteins, Receptors, Estrogen, Recombinant Proteins, Regulatory Sequences, Nucleic Acid, Multivariate Analysis, Gene Silencing, Gene Expression Profiling, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Chromatin Immunoprecipitation, GATA1 Transcription Factor, GATA2 Transcription Factor, Mice, Basic Helix-Loop-Helix Proteins

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