Unraveling Mechanisms of Transcriptional Repression: Novel Insights from Brinker

摘要: Transcriptional repressors bind cis-regulatory elements of target genes in a sequence specific manner. To antagonize transcription, primarily function by recruiting accessory proteins, co-repressors, which turn largely modifying chromatin structure. Although repressor could just single co-repressor, many recruit more than one, with Brinker (Brk) from Drosophila the CtBP and Groucho (Gro), addition to possessing third repression domain, 3R. Previous studies indicated that Gro is sufficient for Brk repress wing imaginal disc, questioning why it should need CtBP, ’short-range’ co-repressor compared can over longer distances. resolve this I have used genomic engineering generate series endogenous brk mutants are unable Gro, and/or 3R domain deleted. Analysis these reveals while recruitment necessary almost make morphologically wild-type fly, insufficient during oogenesis where must utilize pattern egg-shell appropriately. insufficiency be explained its downregulation Brk-expressing cells through phosphorylation downstream EGFR signaling, thus making unavailable then resort repressive activity. The present study dissects mechanism activity transcription factor co-repressors first do so multicellular eukaryotes physiologically relevant manner; additionally findings provide better understanding factors general may one co-repressor.