Antagonism of FOG-1 and GATA factors in fate choice for the mast cell lineage
| Autor: | Koichi Akashi, Stuart H. Orkin, Hirokazu Shigematsu, Tyler B. Moran, Alan B. Cantor, Yojiro Arinobu, Matthew R. Sullivan, Hiromi Iwasaki |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Lineage (genetic) Cellular differentiation Immunology Bone Marrow Cells Mice Transgenic Cell fate determination Biology Article Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Immunology and Allergy GATA1 Transcription Factor Mast Cells Progenitor cell Enhancer Transcription factor Embryonic Stem Cells Yolk Sac 030304 developmental biology Mice Knockout Zinc finger transcription factor 0303 health sciences Multipotent Stem Cells Nuclear Proteins Cell Differentiation Articles Mast cell Molecular biology Mice Mutant Strains Cell biology GATA2 Transcription Factor Mice Inbred C57BL medicine.anatomical_structure 030220 oncology & carcinogenesis Transcription Factors |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| DOI: | 10.1084/jem.20070544 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|