Long- and Short-Range Transcriptional Repressors Induce Distinct Chromatin States on Repressed Genes
Long- and Short-Range Transcriptional Repressors Induce Distinct Chromatin States on Repressed Genes
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DOI：
10.1016/j.cub.2011.01.054
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发表时间：
2011-03-08
期刊：
影响因子：
9.2
通讯作者：
Arnosti, David N.
中科院分区：
文献类型：
--
作者：
Li, Li M.;Arnosti, David N.
转录抑制对于在发育过程中建立精确的基因表达模式至关重要[1]。根据作用范围的不同，控制果蝇早期节段的抑制因子可以分为短期或长期因素，既可以局部抑制相邻的激活物，也可以广泛地沉默整个基因座[2]。矛盾的是，这些抑制子招募了共同的辅阻遏子Groucho和CtBP，尽管它们的抑制范围不同[3-7]。为了揭示这两种不同的抑制模式背后的机制，我们使用了典型的远程抑制因子头发和短程抑制因子Knirps进行了染色质分析。染色质免疫沉淀和微球菌核酸酶图谱研究表明，Knirps引起局部组蛋白密度和乙酰化的改变，并抑制激活剂的招募，而不影响基础转录机制的招募。相反，毛发诱导广泛的组蛋白去乙酰化，并抑制基础机械的招募，而不诱导染色质紧致。我们的研究提供了详细的机制洞察对选定的内源性靶基因的短期和长期抑制，并建议转录辅阻遏子可以不同的部署，以上下文相关的方式介导染色质的变化。
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 CtBP, 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 widespread histone deacetylation and inhibits the recruitment of basal machinery without inducing chromatin compaction. Our study provides detailed mechanistic insight 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.