FOG-2, a Heart- and Brain-Enriched Cofactor for GATA Transcription Factors

Abstract

Members of the GATA family of zinc finger transcription factors have been shown to play important roles in the control of gene expression in a variety of cell types. GATA-1, -2, and -3 are expressed primarily in hematopoietic cell lineages and are required for proliferation and differentiation of multiple hematopoietic cell types, whereas GATA-4, -5, and -6 are expressed in the heart, where they activate cardiac muscle structural genes. Friend of GATA-1 (FOG) is a multitype zinc finger protein that interacts with GATA-1 and serves as a cofactor for GATA-1-mediated transcription. FOG is coexpressed with GATA-1 in developing erythroid and megakaryocyte cell lineages and cooperates with GATA-1 to control erythropoiesis. We describe a novel FOG-related factor, FOG-2, that is expressed predominantly in the developing and adult heart, brain, and testis. FOG-2 interacts with GATA factors, and interaction of GATA-4 and FOG-2 results in either synergistic activation or repression of GATA-dependent cardiac promoters, depending on the specific promoter and the cell type in which they are tested. The properties of FOG-2 suggest its involvement in the control of cardiac and neural gene expression by GATA transcription factors.

ACKNOWLEDGMENTS

We thank Stuart Orkin for providing reagents and communicating results prior to publication. We also acknowledge A. Tizenor for assistance with graphics, W. Simpson for editorial assistance, J. Starke and R. Wells for histologic preparations, and Zhi-Ping Liu for two-hybrid constructs.

This work was supported by grants from NIH, the Robert A. Welch Foundation, the Texas Advanced Technology Program, and the American Heart Association to E.N.O.

ADDENDUM IN PROOF

After submission of this paper, two other papers described the cloning of FOG-2: one by Tevosian et al. (S. Tevosian, A. Deconinck, A. Cantor, H. Hir, Y. Fujiwara, G. Corfas, and S. H. Orkin, Proc. Natl. Acad. Sci. USA 96:950–955, 1999) and one by Sevensson et al. (E. C. Sevensson, R. L. Tufts, C. E. Polk, and J. M. Leiden, Proc. Natl. Acad. Sci. USA 96:956–961, 1999).