Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex.
Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex.
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DOI：
10.1038/s41467-023-43968-8
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发表时间：
2023-12-08
影响因子：
16.6
通讯作者：
Farnung, Lucas
中科院分区：
文献类型：
--
作者：
Markert, Jonathan W.;Vos, Seychelle M.;Farnung, Lucas
组蛋白乙酰化是指导基因表达调控的关键翻译后修饰。在酵母中，含有Rpd3S复合物的I类组蛋白去乙酰化酶通过去除活性转录基因中的组蛋白乙酰化，在抑制假转录中起关键作用。葡萄球菌Rpd3S复合体有5个亚基（Rpd3、Sin3、Rco1、Eaf3和Ume1），但其亚基化学计量学以及该复合体如何与核小体结合以实现底物特异性尚不清楚。在这里，我们报告了完整的Rpd3S复合物结合核小体的低温电镜结构。Sin3和两个拷贝的亚基Rco1和Eaf3包围去乙酰化酶亚基Rpd3，协调Ume1的定位。Rpd3S复合体在赖氨酸36位置结合三甲基化的H3尾部，并与核小体DNA和H2A-H2B酸性斑块进行多次额外接触。通过Sin3亚基坐标结合乙酰化组蛋白底物来实现底物特异性的直接调控。在这项研究中，作者展示了与核小体结合的Rpd3S复合物的低温电镜重建。相应的模型描述了Rpd3S复合物促进基因体内组蛋白去乙酰化的相互作用。
Acetylation of histones is a key post-translational modification that guides gene expression regulation. In yeast, the class I histone deacetylase containing Rpd3S complex plays a critical role in the suppression of spurious transcription by removing histone acetylation from actively transcribed genes. The S. cerevisiae Rpd3S complex has five subunits (Rpd3, Sin3, Rco1, Eaf3, and Ume1) but its subunit stoichiometry and how the complex engages nucleosomes to achieve substrate specificity remains elusive. Here we report the cryo-EM structure of the complete Rpd3S complex bound to a nucleosome. Sin3 and two copies of subunits Rco1 and Eaf3 encircle the deacetylase subunit Rpd3 and coordinate the positioning of Ume1. The Rpd3S complex binds both trimethylated H3 tails at position lysine 36 and makes multiple additional contacts with the nucleosomal DNA and the H2A–H2B acidic patch. Direct regulation via the Sin3 subunit coordinates binding of the acetylated histone substrate to achieve substrate specificity. In this study, the authors present the cryogenic electron microscopy reconstruction of the Rpd3S complex engaged with a nucleosome. The corresponding model describes the interactions that facilitate histone deacetylation within gene bodies by the Rpd3S complex.
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影响因子：
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作者：
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通讯作者：
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