ZEB represses transcription through interaction with the corepressor CtBP

ZEB is an active transcriptional repressor that regulates lymphocyte and mu scle differentiation in vertebrates. its homologue in Drosophila (zfh-1) is also essential for differentiation of somatic and cardiac muscle. Here, we demonstrate that ZEE and zfh-1 interact with the corepressor CtBP to repre ss transcription. ZEE and zfh-1,both contain the sequence PLDLS in the same region of the repressor domain, and we demonstrate that this sequence bind s CtBP-1 and -2. In vertebrate species, ZEE contains two additional CtBP-li ke binding sites (variations of the PLDLS sequence) that also bind CtBP pro teins and are required for full repressor activity, The three sites have an additive effect, and mutation of all three sites is necessary to abolish b oth binding to CtBP and repressor activity. Finally, we demonstrate that th e interaction of CtBP with ZEE at the promoter is necessary for repressor a ctivity.