Transcriptional repression has been implicated in normal biological processes (e.g. animal embryogenesis) and pathological processes (e.g. tumorigenesis). However, the mechanisms of transcriptional repression are still poorly understood. The overall goal of the proposed research is to determine whether short-range and long-range repression represent distinct mechanisms of transcriptional repression in the early Drosophila embryo. Most of the experiments will be conducted in the context of a simple model, whereby the newly identified dCtBP corepressor protein mediates short-range repression, while the Groucho corepressor mediates long-range repression. The research plan includes two specific aims: (i) characterization of Snail-mediated repression by misexpressing Snail and the mutated derivatives lacking the dCtBP interaction motifs (P-DLS-K/R) and by identifying corepressor proteins; and (ii) characterization of Hairy-mediated repression, by misexpressing Gal4-Halry, Snail-Hairy and the mutated Hairy derivatives lacking the dCtBP interaction motif (P-SLV-K) or Groucho interaction motif (WRPW), to determine whether Hairy functions either as a short- range or long-range repressor, respectively.
