Long- and Short-Range Transcriptional Repressors Induce Distinct Chromatin States on Repressed Genes

Abstract

Summary Transcriptional repression is essential for establishing precise patterns of gene expression during development [1]. Repressors governing early Drosophila segmentation can be classified as short- or long-range factors based on their ranges of action, acting either locally to quench adjacent activators, or broadly to silence an entire locus [2]. Paradoxically, these repressors recruit common corepressors, Groucho and dCtBP, despite their different ranges of repression [3–7]. To reveal the mechanisms underlying these two distinct modes of repression, we performed chromatin analysis, using the prototypical long-range repressor Hairy and the short-range repressor Knirps. Chromatin immunoprecipitation and micrococcal nuclease mapping studies reveal that Knirps causes local changes of histone density and acetylation, and the inhibition of activator recruitment, without affecting the recruitment of basal transcriptional machinery. In contrast, Hairy induces wide-spread histone deacetylation and inhibits the recruitment of basal machinery without inducing chromatin compaction. Our study provides detailed mechanistic information into short- and long-range repression on selected endogenous target genes, and suggests that the transcriptional corepressors can be differentially deployed to mediate chromatin changes in a context-dependent manner.

The Central Region of the Drosophila Co-repressor Groucho as a Regulatory Hub

“…Gro-mediated repression may be associated with changes in chromatin structure, including histone deacetylation and possibly increased nucleosome density (3,18,54). Consistent with this possibility, our proteomic screen identified a number of histone modifiers and ATP-dependent chromatin remodelers, including subunits of the ACF chromatin remodeling complexes (Acf1 and Iswi), the histone chaperone NAP1, and the histone kinases JIL-1 and Ball.…”

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

“…Transcriptional repressors such as Dl have been reported to reduce the occupancy of transcription factors and remove histone acetylation through the recruitment of corepressors and histone deacetylases (Chen et al 1999;Kulkarni and Arnosti 2005;Sekiya and Zaret 2007;Winkler et al 2010;Li and Arnosti 2011). Thus, the low levels of H3K27ac and the reduced access to transcription factors that we observe for zen, dpp, and tld must be to some extent the result of Dl-mediated repression.…”

Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription

“…This suggests that pausing allows plasticity in gene expression during development. Transient repression can be mediated by repressors like Snail, Knirps, Runt, and Ftz, which appear to act by inhibiting the release of paused polymerases into productive elongation (Wang et al 2007;Bothma et al 2011;Li and Arnosti 2011). As a result, these genes will be poised for reactivation following relief of repression.…”