Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection
Distinct roles of HDAC complexes in promoter silencing, antisense suppression and DNA damage protection
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DOI：
10.1038/nsmb1239
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发表时间：
2007-05-01
影响因子：
16.8
通讯作者：
Grewal, Shiv I. S.
中科院分区：
文献类型：
--
作者：
Nicolas, Estelle;Yamada, Takatomi;Grewal, Shiv I. S.
组蛋白乙酰化在调节DNA可及性中是重要的。多功能Sin3蛋白结合组蛋白脱乙酰酶（HDAC）以组装选择性靶向染色质的沉默复合物。我们发现，在裂变酵母，一个必不可少的HDAC，Clr6，存在于两个不同的Sin3核心复合物。复合物I包含一个重要的Sin3同源物，Pst 1和其他因子，主要靶向基因启动子。复合物II包含一个非必需的Sin3同系物，Pst 2，和几个保守的蛋白质。它优先靶向转录的染色体区域和着丝粒核心。复合物II的缺陷消除了染色质的全局保护功能，导致DNA对基因毒性剂和由外泌体加工的广泛反义转录物的可及性增加。值得注意的是，这两个Clr6复合物差异抑制正向和反向着丝粒重复转录，这表明这些复合物以类似的方式调节异染色质和常染色质中的转录，包括抑制来自隐蔽起始位点的假转录。
Histone acetylation is important in regulating DNA accessibility. Multifunctional Sin3 proteins bind histone deacetylases (HDACs) to assemble silencing complexes that selectively target chromatin. We show that, in fission yeast, an essential HDAC, Clr6, exists in two distinct Sin3 core complexes. Complex I contains an essential Sin3 homolog, Pst1, and other factors, and predominantly targets gene promoters. Complex II contains a nonessential Sin3 homolog, Pst2, and several conserved proteins. It preferentially targets transcribed chromosomal regions and centromere cores. Defects in complex II abrogate global protective functions of chromatin, causing increased accessibility of DNA to genotoxic agents and widespread antisense transcripts that are processed by the exosome. Notably, the two Clr6 complexes differentially repress forward and reverse centromeric repeat transcripts, suggesting that these complexes regulate transcription in heterochromatin and euchromatin in similar manners, including suppression of spurious transcripts from cryptic start sites.