FOG acts as a repressor of red blood cell development in Xenopus

Members of the GATA family of zinc-finger transcription factors have critic al roles in a variety of cell types. GATA-1, GATA-2 and GATA-3 are required for proliferation and differentiation of several hematopoietic lineages, w hereas GATA-4, GATA-5 and GATA-6 activate cardiac and endoderm gene express ion programs, Two GATA cofactors have recently been identified, Friend of G ATA-1 (FOG-1) interacts with GATA-1 and is expressed principally in hematop oietic lineages, whereas FOG-2 is expressed predominantly in heart and brai n. Although gene targeting experiments are consistent with an essential rol e for FOG-1 as an activator of GATA-1 function, reporter assays in transfec ted cells indicate that FOG-I and FOG-2 can act as repressors, We have clon ed a Xenopus laevis homologue of FOG that is structurally most similar to F OG-I, but is expressed predominantly in heart and brain, as well as the ven tral blood island and adult spleen. Ectopic expression and explant assays d emonstrate that FOG proteins can act as repressors in vivo, in part through interaction with the transcriptional co-repressor, C-terminal Binding Prot ein (CtBP), FOG may regulate the differentiation of red blood cells by modu lating expression and activity of GATA-1 and GATA-2 We propose that the FOG proteins participate in the switch from progenitor proliferation to red bl ood cell maturation and differentiation.