The tumor suppressor protein CTBP mediates short-range repression in the Drosophila embryo

The segmentation gene even-skipped (eve) is regulated by a complex promoter region that contains a series of enhancers which control the expression of individual stripes. Short-range transcriptional repression permits this enhancer autonomy, in that repressers bound to one of the stripe enhancers do not interfere with the expression of the other enhancers in the eve promoter region. Not all repressers are short-range, for example, dorsal and hairy, can function over distances of 1 kb or more to mediate the dominant silencing of a complex promoter region. Evidence will be presented that short-range and long-range repressers work through distinct corepressor proteins. In particular, the Drosophila homolog of the human CtBP protein (dCtBP) is shown to be a corepressor of two unrelated shortrange repressors, snail and knirps. and might also participate in Kruppelmediated repression. These disparate repressors contrain a related sequence motif, P-DLS-K, which is essential for repressor-dCtBP interactions. Mutations in this sequence block knirps-mediated repression in transgenic Drosophila embryos. Moreover, a P-induced mutation in dCtBP exhibits gene-dosage interactions with a null mutation in knirps. Different models for repression will be discussed.