Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage

Alan B. Cantor, Hiromi Iwasaki, Yojiro Arinobu, Tyler B. Moran, Hirokazu Shigematsu, Matthew R. Sullivan, Koichi Akashi, Stuart H. Orkin

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

The zinc finger transcription factor GATA-1 requires direct physical interaction with the cofactor friend of GATA-1 (FOG-1) for its essential role in erythroid and megakaryocytic development. We show that in the mast cell lineage, GATA-1 functions completely independent of FOG proteins. Moreover, we demonstrate that FOG-1 antagonizes the fate choice of multipotential progenitor cells for the mast cell lineage, and that its downregulation is a prerequisite for mast cell development. Remarkably, ectopic expression of FOG-1 in committed mast cell progenitors redirects them into the erythroid, megakaryocytic, and granulocytic lineages. These lineage switches correlate with transcriptional down-regulation of GATA-2, an essential mast cell GATA factor, via switching of GATA-1 for GATA-2 at a key enhancer element upstream of the GATA-2 gene. These findings illustrate combinatorial control of cell fate identity by a transcription factor and its co factor, and highlight the role of transcriptional networks in lineage determination. They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment. JEM

Original languageEnglish
Pages (from-to)611-624
Number of pages14
JournalJournal of Experimental Medicine
Volume205
Issue number3
DOIs
Publication statusPublished - Mar 17 2008

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage'. Together they form a unique fingerprint.

Cite this