| First Author | Cantor AB | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 3 | Pages | 611-24 |
| PubMed ID | 18299398 | Mgi Jnum | J:133105 |
| Mgi Id | MGI:3777731 | Doi | 10.1084/jem.20070544 |
| Citation | Cantor AB, et al. (2008) Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage. J Exp Med 205(3):611-24 |
| abstractText | 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. |
