Format

Send to

Choose Destination
See comment in PubMed Commons below
J Exp Med. 2008 Mar 17;205(3):611-24. doi: 10.1084/jem.20070544. Epub 2008 Feb 25.

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

Author information

1
Division of Pediatric Hematology/Oncology, Children's Hospital Boston, Boston, MA 02115, USA. alan.cantor@childrens.harvard.edu

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 down-regulation 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 cofactor, and highlight the role of transcriptional networks in lineage determination. They also provide evidence for lineage instability during early stages of hematopoietic lineage commitment.

PMID:
18299398
PMCID:
PMC2275384
DOI:
10.1084/jem.20070544
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center