Transcriptional repression by Suppressor of Hairless involves the binding of a Hairless-dCtBP complex in Drosophila

Notch is the receptor for a conserved signaling pathway that regulates nume rous cell fate decisions during development Ill, Signal transduction involv es the presenilin-dependent intracellular processing of Notch and the nucle ar translocation of the intracellular domain of Notch, NICD [2-6]. NICD ass ociates with Suppressor of Hairless [Su(H)] a DNA binding protein, and Mast ermind (Mam), a transcriptional coactivator [7-9], In the absence of Notch signaling, Su(H) acts as a transcriptional repressor [10, 11]. Repression b y Su(H) is relieved by the activation of Notch [12-16]. In the Drosophila e mbryo, this transcriptional switch from repression to activation is importa nt for patterning the expression of the single-minded (sim) gene along the dorsoventral axis [12]. Here, we investigate the mechanisms by which Su(H) inhibits the expression of Notch target genes in Drosophila. We show that H airless, an antagonist of Notch signaling [17-19], is required to repress t he transcription of the sim gene. Hairless forms a DNA-bound complex with S u(H), Furthermore, it directly binds the Drosophila C-terminal Binding Prot ein (dCtBP), which acts as a transcriptional corepressor. The dCtBP binding motif of Hairless is essential for the function of Hairless in vivo. We pr opose that Hairless mediates transcriptional repression by Su(H) via the re cruitment of dCtBP.