ZFIN ID: ZDB-PUB-110524-32
Genome-wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators
Tijssen, M.R., Cvejic, A., Joshi, A., Hannah, R.L., Ferreira, R., Forrai, A., Bellissimo, D.C., Oram, S.H., Smethurst, P.A., Wilson, N.K., Wang, X., Ottersbach, K., Stemple, D.L., Green, A.R., Ouwehand, W.H., and Göttgens, B.
Date: 2011
Source: Developmental Cell   20(5): 597-609 (Journal)
Registered Authors: Stemple, Derek L.
Keywords: none
MeSH Terms:
  • Basic Helix-Loop-Helix Transcription Factors/metabolism*
  • Binding Sites
  • Cell Differentiation
  • Cells, Cultured
  • Core Binding Factor Alpha 2 Subunit/metabolism*
  • GATA1 Transcription Factor/metabolism*
  • GATA2 Transcription Factor/metabolism*
  • Genome, Human/genetics*
  • Humans
  • Megakaryocytes/cytology
  • Megakaryocytes/metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Proto-Oncogene Protein c-fli-1/metabolism*
  • Proto-Oncogene Proteins/metabolism*
PubMed: 21571218 Full text @ Dev. Cell
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.