FOG is a multitype zinc finger protein that is essential for megakaryopoiesis, binds to the amino-terminal finger of GATA-1, and modulates the transcription of GATA-1 target genes. Presently investigated are effects of FOG and GATA-1 on the transcription of the megakaryocytic integrin gene, alpha IIb. In GATA-1-deficient FDCER cells (in the presence of endogenous FOG), ectopically expressed GATA-1 activated transcription 3-10-fold both from alpha IIb templates and the endogenous alpha IIb gene. The increased expression of FOG increased reporter construct transcription 30-fold overall. Unexpectedly, alphaIIb gene transcription also was stimulated efficiently upon the ectopic expression in of FOG per se. This occurred in the absence of any detectable expression of GATA-1 and was observed in multiple independent sublines for both the endogenous alpha IIb gene and transfected constructs yet proved to depend largely upon conserved GATA elements 457 and 55 base pairs upstream from the transcriptional start site. In 293 cells, FOG plus GATA-1 but not FOG alone only moderately stimulated alpha IIb transcription, and no direct interactions of FOG with the alpha IIb promoter were detectable. Thus, FOG acts in concert with GATA-1 to stimulate alpha IIb expression but also can act via a GATA-1-independent route, which is proposed to involve additional hematopoietic-restricted cofactors (possibly GATA-2).