Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration

Genome Res. 2011 Oct;21(10):1659-71. doi: 10.1101/gr.125088.111. Epub 2011 Jul 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Differentiation / genetics*
  • Cell Line
  • Chromatin Assembly and Disassembly
  • Chromatin Immunoprecipitation
  • Epigenesis, Genetic*
  • Erythropoiesis / genetics*
  • Estradiol / pharmacology
  • Estradiol / physiology
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / metabolism*
  • GATA2 Transcription Factor / metabolism
  • Gene Expression Profiling
  • Gene Silencing
  • Mice
  • Multivariate Analysis
  • Peptide Hydrolases / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Estrogen / genetics
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid
  • T-Cell Acute Lymphocytic Leukemia Protein 1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Gata1 protein, mouse
  • Gata2 protein, mouse
  • Proto-Oncogene Proteins
  • Receptors, Estrogen
  • Recombinant Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Tal1 protein, mouse
  • Estradiol
  • Peptide Hydrolases
  • histonase

Associated data

  • GEO/GSE30142