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Molecular and Cellular Biology, June 2002, p. 4268-4279, Vol. 22, No. 12
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.12.4268-4279.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Distinct Domains of the GATA-1 Cofactor FOG-1 Differentially Influence Erythroid versus Megakaryocytic Maturation

Alan B. Cantor,1 Samuel G. Katz,1,2 and Stuart H. Orkin1,2*

Division of Hematology/Oncology, Children's Hospital and Dana-Farber Cancer Institute, Department of Pediatrics, Harvard Medical School,1 Howard Hughes Medical Institute, Children's Hospital, Boston, Massachusetts 021152

Received 5 December 2001/ Accepted 13 March 2002

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.

* Corresponding author. Mailing address: Division of Hematology, Children's Hospital Medical Center, 320 Longwood Ave., Boston, MA 02115. Phone (617) 355-8178. Fax: (617) 738-5922. E-mail: orkin{at}bloodgroup.tch.harvard.edu.

Molecular and Cellular Biology, June 2002, p. 4268-4279, Vol. 22, No. 12
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.12.4268-4279.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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