zfh-1, the Drosophila homologue of ZEB, is a transcriptional repressor that regulates somatic myogenesis

zfh-1 is a member of the zfh family of proteins, which all contain zinc fin ger and homeodomains. The roles and mechanisms of action of most family mem bers are still unclear. However, we have shown previously that another memb er of the family, the vertebrate ZEE protein, is a transcriptional represso r that binds E box sequences and inhibits myotube formation in cell culture assays. zfh-1 is downregulated in Drosophila embryos prior to myogenesis, Embryos with zfh-1 loss of-function mutation show alterations in the number and position of embryonic somatic muscles, suggesting that zfh-1 could hav e a regulatory role in myogenesis. However, nothing is known about the natu re or mechanism of action of zfh-1, Here, we demonstrate that zfh-1 is a tr anscription factor that binds E box sequences and acts as an active transcr iptional repressor, When zfh-1 expression was maintained in the embryo beyo nd its normal temporal pattern of downregulation, the differentiation of so matic but not visceral muscle was blocked. One potential target of zfh-1 in somatic myogenesis could be the myogenic factor mef2, mef2 is known to be regulated by the transcription factor twist, and we show here that zfh-1 hi nds to sites in the mef2 upstream regulatory region and inhibits twist tran scriptional activation. Even though there is little sequence similarity in the repressor domains of ZEE and zfh-1, we present evidence that zfh-1 is t he functional homologue of ZEE and that the role of these proteins in myoge nesis is conserved from Drosophila to mammals.