SELF-ASSOCIATION OF THE ERYTHROID TRANSCRIPTION FACTOR GATA-1 MEDIATED BY ITS ZINC-FINGER DOMAINS

GATA-1, the founding member of a distinctive family of transcription f actors, is expressed predominantly in erythroid cells and participates in the expression of numerous erythroid cell-expressed genes. GATA-bi nding sites are found in the promoters and enhancers of globin and non globin erythroid genes as well as in the alpha-and beta-globin locus c ontrol regions. To elucidate how GATA-1 may function in a variety of r egulatory contexts, we have examined its protein-protein interactions. Here we show that GATA-1 self-associates in solution and in whole-cel l extracts and that the zinc finger region of the molecule is sufficie nt to mediate this interaction, This physical interaction can influenc e transcription, as GATA-1 self-association is able to recruit a trans criptionally active but DNA-binding-defective derivative of GATA-1 to promoter-bound GATA-1 and result in superactivation. Through in vitro studies with bacterially expressed glutathione S-transferase fusion pr oteins, we have localized the minimal domain required for GATA-1 self- association to 40 amino acid residues within the C-terminal zinc finge r region. Finally, we have detected physical interaction of GATA-1 wit h other GATA family members (GATA-2 and GATA-3) also mediated through the zinc finger domain. These findings have broad implications for the involvement of GATA factors in transcriptional control. In particular , the interaction of GATA-1 with itself and with other transcription f actors may facilitate its function at diverse promoters in erythroid c ells and also serve to bring together, or stabilize, loops between dis tant regulatory elements, such as the globin locus control regions and downstream globin promoters. We suggest that the zinc finger region o f GATA-1, and related proteins, is multifunctional and mediates not on ly DNA binding but also important protein-protein interactions.