GATA-4 ACTIVATES TRANSCRIPTION VIA 2 NOVEL DOMAINS THAT ARE CONSERVEDWITHIN THE GATA-4 5/6 SUBFAMILY/

GATA-4 is one of the earliest developmental markers of the precardiac mesoderm, heart, and gut and has been shown to activate regulatory ele ments controlling transcription of genes encoding cardiac-specific pro teins, To elucidate the molecular mechanisms underlying the transcript ional activity of the GATA-4 protein, structure-function analyses were performed. These analyses revealed that the C-terminal zinc finger an d adjacent basic domain of GATA-4 is bifunctional, modulating both DNA -binding and nuclear localization activities, The N terminus of the pr otein encodes two independent transcriptional Activation Domains (amin o acids 1-74 and amino acids 130-177). Amino acid residues were identi fied within each domain that are required for transcriptional activati on, Finally, we have shown that regions of Xenopus GATA-5 and -6 corre sponding to Activation Domains I and II, respectively, function as pot ent transcriptional activators. The identification and functional char acterization of two evolutionarily conserved transcriptional Activatio n Domains within the GATA-4/5/6 subfamily suggests that each of these domains modulates critical functions in the transcriptional regulatory program(s) encoded by GATA-4, -5, and -6 during vertebrate developmen t. As such these data provide novel insights into the molecular mechan isms that control development of the heart.