Transcriptional repression is essential for establishing localized stripes, bands, and tissue-specific patterns of gene expression in the early embryo. DNA-binding repressors can be classified into two groups. Long-range repressors, Hairy (bHLH) and Dorsal (rel domain, NF-kB), can function over distances of >1 kb to silence the transcription complex and inhibit multiple enhancers, thereby resulting in simple on/off patterns of gene expression. Groucho is a corepressor of the long-range repressors and interacts with Drosophila Rpd3 histone deacetylase. Short-range repressors, Kruppel (zinc finger), Knirps (nuclear hormone receptor), Snail (zinc finger), and Giant (bZIP), work over distances of less than 100 bp to inhibit adjacent activators or the core promoter complex. This form of repression permits enhancers to work independently of one another to direct complex, additive patterns of gene expression, including seven-stripe patterns of even-skipped (eve) and hairy expression. The eve gene expression is regulated by five enhancers and each of them controls one or two stripes. Short-range repression allows the conversion of the broad input (Bicoid, D-STAT, and perhaps Caudal) into the sharp output (seven stripes) without letting the enhancers interfere with each other. The borders of individual stripes are formed by localized short-range repressors. We have identified and characterized a corepressor protein, Drosophila CtBP (dCtBP), that interacts with four unrelated short-range repressors. We recently found that a corepressor dDrap1 also mediates short-range repression. In addition, another putative corepressor is being isolated. Therefore, it currently appears that three corepressors mediate short-range repression and one corepressor mediates long-range repression. We will employ a combination of genetic, biochemical, and molecular biological approaches to reveal how the range of action is regulated.
Key Words: transcriptional repression, Drosophila, embryo, dCtBP, dDrap1, corepressor, pattern formation, gene regulation.