Beschreibung:
Transcriptional repressors employ a variety of mechanisms to regulate eukaryotic gene expression, and research from the Drosophila embryo has highlighted two distinct functional classes of repressor. Short‐range repressors such as Knirps work locally to interfere with proximal transcription factors, and others, such as the HES family protein Hairy, dominantly repress transcription of an entire locus with multiple regulatory elements. Both classes of repressor interact with common corepressors such as the evolutionarily conserved C‐terminal binding protein CtBP and WD‐40 domain protein Groucho. The basis and importance of such complexity is unknown, however it is possible that these types of repressors may exert unique effects in a gene‐specific manner. Our previous studies have highlighted the very localized chromatin modifications induced by the Knirps short‐range repressor, contrasted with kbp‐wide alterations observed with Hairy, however these studies were limited to individual target genes, leaving open the question about gene specificity, and whether repressors exert the same effect on all loci, regardless of gene activity or activator inputs. We have now analyzed the impact of Knirps and Hairy repression on a genome‐wide basis. We observe strong indications of correlated chromatin modifications on a wide set of targets, for instance, both H3K4 and H3K27 acetylation are coordinately reduced at Hairy targets, showing changes over a range an average of ~2kbp (often up to 10 kbp). A subset of targeted genes lacks significant deacetylation marks, but reveals strong upregulation of H3K9 trimethylation, as well as increased occupancy of histone H1 on the gene body. Our initial analysis indicates that complex and diverse repression pathways may be tailored to specific gene contexts, permitting a uniform control of heterogeneously regulated genes.Grant Funding Source: Supported by NIH GMS 056976