The mammalian transcriptional repressor RBP (CBF1) targets TFIID and TFIIA to prevent activated transcription

RBP is a cellular protein that functions as a transcriptional repressor in mammalian cells. REP has elicited great interest lately because of its established roles in regulating gene expression, in Drosophila and mouse development, and as a component of the Notch signal transduction pathway. This report focuses on the mechanism by which REP represses transcription and thereby regulates expression of a relatively simple, but natural, promoter. The results show that, irrespective of the close proximity between REP and other transcription factors bound to the promoter, REP does not occlude binding by these other transcription factors. Instead, REP interacts with two transcriptional coactivators: dTAF(II)110, a subunit of TEIID, and TFIIA to repress transcription. The domain of dTAF(II)110 targeted by REP is the same domain that interacts with TPIIA, but is disparate from the domain that interacts with Sp1. Repression can be thwarted when stable transcription preinitiation complexes are formed before REP addition, suggesting that REP interaction with TFIIA and TFIID perturbs optimal interactions between these coactivators. Consistent with this, interaction between RBP and TFIIA precludes interaction with dTAF(II)110. This is the first report of a repressor specifically targeting these two coactivators to subvert activated transcription.