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

Research output: Contribution to journalArticle

248 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)667-681
Number of pages15
JournalMolecular Cell
Volume36
Issue number4
DOIs
StatePublished - Nov 25 2009

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GATA Transcription Factors
Chromatin
Hematopoiesis
Genome
Co-Repressor Proteins
Erythroid Cells
Nucleotide Motifs

Keywords

  • DNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Fujiwara, T., O'Geen, H., Keles, S., Blahnik, K., Linnemann, A. K., Kang, Y. A., ... Bresnick, E. H. (2009). Discovering Hematopoietic Mechanisms through Genome-wide Analysis of GATA Factor Chromatin Occupancy. Molecular Cell, 36(4), 667-681. https://doi.org/10.1016/j.molcel.2009.11.001

Discovering Hematopoietic Mechanisms through Genome-wide Analysis of GATA Factor Chromatin Occupancy. / Fujiwara, Tohru; O'Geen, Henriette; Keles, Sunduz; Blahnik, Kimberly; Linnemann, Amelia K.; Kang, Yoon A.; Choi, Kyunghee; Farnham, Peggy J.; Bresnick, Emery H.

In: Molecular Cell, Vol. 36, No. 4, 25.11.2009, p. 667-681.

Research output: Contribution to journalArticle

Fujiwara, T, O'Geen, H, Keles, S, Blahnik, K, Linnemann, AK, Kang, YA, Choi, K, Farnham, PJ & Bresnick, EH 2009, 'Discovering Hematopoietic Mechanisms through Genome-wide Analysis of GATA Factor Chromatin Occupancy', Molecular Cell, vol. 36, no. 4, pp. 667-681. https://doi.org/10.1016/j.molcel.2009.11.001
Fujiwara, Tohru ; O'Geen, Henriette ; Keles, Sunduz ; Blahnik, Kimberly ; Linnemann, Amelia K. ; Kang, Yoon A. ; Choi, Kyunghee ; Farnham, Peggy J. ; Bresnick, Emery H. / Discovering Hematopoietic Mechanisms through Genome-wide Analysis of GATA Factor Chromatin Occupancy. In: Molecular Cell. 2009 ; Vol. 36, No. 4. pp. 667-681.
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