Discovering Hematopoietic Mechanisms through Genome-wide Analysis of GATA Factor Chromatin Occupancy

Tohru Fujiwara, Henriette O'Geen, Sunduz Keles, Kimberly Blahnik, Amelia K. Linnemann, Yoon A. Kang, Kyunghee Choi, Peggy J. Farnham, Emery H. Bresnick

研究成果: Article査読

271 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)667-681
ページ数15
ジャーナルMolecular Cell
36
4
DOI
出版ステータスPublished - 2009 11 25
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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