Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: Role of Ets transcription factors

Xun Wang, John D. Crispino, Danielle L. Letting, Minako Nakazawa, Mortimer Poncz, Gerd A. Blobel

Research output: Contribution to journalArticlepeer-review

116 Scopus citations

Abstract

The transcription factor GATA-1 and its cofactor FOG-1 are essential for the normal development of erythroid cells and megakaryocytes. FOG-1 can stimulate or inhibit GATA-1 activity depending on cell and promoter context. How the GATA-1-FOG-1 complex controls the expression of distinct sets of gene in megakaryocytes and erythroid cells is not understood. Here, we examine the molecular basis for the megakaryocyte-restricted activation of the αIIb gene. FOG-1 stimulates GATA-1-dependent αIIb gene expression in a manner that requires their direct physical interaction. Transcriptional output by the GATA-1-FOG-1 complex is determined by the hematopoietic Ets protein Fli-1 that binds to an adjacent Ets element. Chromatin immunoprecipitation experiments show that GATA-1, FOG-1 and Fli-1 co-occupy the αIIb promoter in vivo. Expression of several additional megakaryocyte-specific genes that bear tandem GATA and Ets elements in their promoters also depends on the physical interaction between GATA-1 and FOG-1. Our studies define a molecular context for transcriptional activation by GATA-1 and FOG-1, and may explain the occurrence of tandem GATA and Ets elements in the promoters of numerous megakaryocyte-expressed genes.

Original languageEnglish (US)
Pages (from-to)5225-5234
Number of pages10
JournalEMBO Journal
Volume21
Issue number19
DOIs
StatePublished - Oct 1 2002

Keywords

  • Ets
  • FOG
  • Fli-1
  • GATA
  • Megakaryocyte

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Control of megakaryocyte-specific gene expression by GATA-1 and FOG-1: Role of Ets transcription factors'. Together they form a unique fingerprint.

Cite this