Discovering hematopoietic mechanisms through genome-wide analysis of GATA factor chromatin occupancy

Mol Cell. 2009 Nov 25;36(4):667-81. doi: 10.1016/j.molcel.2009.11.001.

Abstract

GATA factors interact with simple DNA motifs (WGATAR) to regulate critical processes, including hematopoiesis, but very few WGATAR motifs are occupied in genomes. Given the rudimentary knowledge of mechanisms underlying this restriction and how GATA factors establish genetic networks, we used ChIP-seq to define GATA-1 and GATA-2 occupancy genome-wide in erythroid cells. Coupled with genetic complementation analysis and transcriptional profiling, these studies revealed a rich collection of targets containing a characteristic binding motif of greater complexity than WGATAR. GATA factors occupied loci encoding multiple components of the Scl/TAL1 complex, a master regulator of hematopoiesis and leukemogenic target. Mechanistic analyses provided evidence for crossregulatory and autoregulatory interactions among components of this complex, including GATA-2 induction of the hematopoietic corepressor ETO-2 and an ETO-2-negative autoregulatory loop. These results establish fundamental principles underlying GATA factor mechanisms in chromatin and illustrate a complex network of considerable importance for the control of hematopoiesis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Computational Biology
  • GATA1 Transcription Factor / metabolism*
  • GATA2 Transcription Factor / metabolism*
  • Gene Expression Profiling
  • Genetic Loci
  • Genome, Human / genetics*
  • Hematopoietic System / metabolism*
  • Homeostasis
  • Humans
  • K562 Cells
  • Leukemia / metabolism
  • Leukemia / pathology
  • Mice
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Sequence Analysis, DNA
  • T-Cell Acute Lymphocytic Leukemia Protein 1

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Chromatin
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • GATA2 Transcription Factor
  • GATA2 protein, human
  • Multiprotein Complexes
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • TAL1 protein, human

Associated data

  • GEO/GSE18829