FOG, A MULTITYPE ZINC-FINGER PROTEIN, ACTS AS A COFACTOR FOR TRANSCRIPTION FACTOR GATA-1 IN ERYTHROID AND MEGAKARYOCYTIC DIFFERENTIATION

The hematopoietic transcription factor GATA-1 is essential for develop ment of the erythroid and megakaryocytic lineages. Using the conserved zinc finger DNA-binding domain of GATA-1 in the yeast two-hybrid syst em, we have identified a novel, multitype zinc finger protein, friend of GATA-1 (FOG), which binds GATA-1 but not a functionally inactive mu tant lacking the amino (N) finger. FOG is coexpressed with GATA-1 duri ng embryonic development and in erythroid and megakaryocytic cells. Fu rthermore, FOG and GATA-1 synergistically activate transcription from a hematopoietic-specific regulatory region and cooperate during both e rythroid and megakaryocytic cell differentiation. These findings indic ate that FOG acts as a cofactor for GATA-1 and provide a paradigm for the regulation of cell type-specific gene expression by GATA transcrip tion factors.