CREB-BINDING PROTEIN COOPERATES WITH TRANSCRIPTION FACTOR GATA-1 AND IS REQUIRED FOR ERYTHROID-DIFFERENTIATION

The transcription factor GATA-1 coordinates multiple events during ter minal erythroid cell maturation, GATA-1 participates in the transcript ion of virtually all erythroid-specific genes, blocks apoptosis of pre cursor cells, and controls the balance between proliferation and cell cycle arrest. Prior studies suggest that the function of GATA-1 is med iated in part through association with transcriptional cofactors. CREB -binding protein (CBP) and its close relative p300 serve as coactivato rs for a variety of transcription factors involved in growth control a nd differentiation. We report here that CBP markedly stimulates GATA-1 's transcriptional activity in transient transfection experiments in n onhematopoietic cells. GATA-1 and CBP also coimmunoprecipitate from nu clear extracts of erythroid cells. Interaction mapping pinpoints conta ct sites to the zinc finger region of GATA-1 and to the E1A-binding re gion of CBP. Expression of a conditional form of adenovirus E1A in mur ine erythroleukemia cells blocks differentiation and expression of end ogenous GATA-1 target genes, whereas mutant forms of E1A unable to bin d CBP/p300 have no effect. Our findings add GATA-1, and very likely ot her members of the GATA family, to the growing list of molecules impli cated in the complex regulatory network surrounding CBP/p300.