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Genome-wide analysis of simultaneous GATA1/2, RUNX1, FLI1, and SCL binding in megakaryocytes identifies hematopoietic regulators.

Hematopoietic differentiation critically depends on combinations of transcriptional regulators controlling the development of individual lineages. Here, we report the genome-wide binding sites for the five key hematopoietic transcription factors--GATA1, GATA2, RUNX1, FLI1, and TAL1/SCL--in primary human megakaryocytes. Statistical analysis of the 17,263 regions bound by at least one factor demonstrated that simultaneous binding by all five factors was the most enriched pattern and often occurred near known hematopoietic regulators. Eight genes not previously appreciated to function in hematopoiesis that were bound by all five factors were shown to be essential for thrombocyte and/or erythroid development in zebrafish. Moreover, one of these genes encoding the PDZK1IP1 protein shared transcriptional enhancer elements with the blood stem cell regulator TAL1/SCL. Multifactor ChIP-Seq analysis in primary human cells coupled with a high-throughput in vivo perturbation screen therefore offers a powerful strategy to identify essential regulators of complex mammalian differentiation processes.

Pubmed ID: 21571218

Authors

  • Tijssen MR
  • Cvejic A
  • Joshi A
  • Hannah RL
  • Ferreira R
  • Forrai A
  • Bellissimo DC
  • Oram SH
  • Smethurst PA
  • Wilson NK
  • Wang X
  • Ottersbach K
  • Stemple DL
  • Green AR
  • Ouwehand WH
  • Gƶttgens B

Journal

Developmental cell

Publication Data

May 17, 2011

Associated Grants

  • Agency: Wellcome Trust, Id: 077037/Z/05/Z
  • Agency: Wellcome Trust, Id: 077047/Z/05/Z
  • Agency: Wellcome Trust, Id: 082597/Z/07/Z
  • Agency: Medical Research Council, Id: G0800784
  • Agency: Medical Research Council, Id: G0900951
  • Agency: Medical Research Council, Id: G0900951(91754)
  • Agency: British Heart Foundation, Id: RG/09/012/28096
  • Agency: Medical Research Council, Id:

Mesh Terms

  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Cell Differentiation
  • Cells, Cultured
  • Core Binding Factor Alpha 2 Subunit
  • GATA1 Transcription Factor
  • GATA2 Transcription Factor
  • Genome, Human
  • Humans
  • Megakaryocytes
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins