Distinct domains of the GATA-1 cofactor FOG-1 differentially influence erythroid versus megakaryocytic maturation.
FOG family zinc finger proteins play essential roles in development through physical interaction with GATA factors. FOG-1, like its interacting partner GATA-1, is required for normal differentiation of erythroid and megakaryocytic cells. Here, we have developed a functional assay for FOG-1 based on its ability to rescue erythroid and megakaryocytic maturation of a genetically engineered FOG-1(-/-) cell line. We demonstrate that interaction through only one of FOG-1's four GATA-binding zinc fingers is sufficient for rescue, providing evidence against a model in which FOG-1 acts to bridge multiple GATA-binding DNA elements. Importantly, we find that distinct regions of FOG-1 differentially influence erythroid versus megakaryocyte maturation. As such, we propose that FOG-1 may modulate the fate of a bipotential erythroid/megakaryocytic precursor cell.
Cantor
Alan B
AB
Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Katz
Samuel G
SG
Orkin
Stuart H
SH
D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008533:Megakaryocytes / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012190:Retroviridae / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism; D016335:Zinc Fingers
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C107310:Zfpm1 protein, mouse