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-Structure paper
Title | Diverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S. |
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Journal, issue, pages | Nature, Vol. 620, Issue 7974, Page 669-675, Year 2023 |
Publish date | Jul 19, 2023 |
Authors | Haipeng Guan / Pei Wang / Pei Zhang / Chun Ruan / Yutian Ou / Bo Peng / Xiangdong Zheng / Jianlin Lei / Bing Li / Chuangye Yan / Haitao Li / |
PubMed Abstract | Context-dependent dynamic histone modifications constitute a key epigenetic mechanism in gene regulation. The Rpd3 small (Rpd3S) complex recognizes histone H3 trimethylation on lysine 36 (H3K36me3) ...Context-dependent dynamic histone modifications constitute a key epigenetic mechanism in gene regulation. The Rpd3 small (Rpd3S) complex recognizes histone H3 trimethylation on lysine 36 (H3K36me3) and deacetylates histones H3 and H4 at multiple sites across transcribed regions. Here we solved the cryo-electron microscopy structures of Saccharomyces cerevisiae Rpd3S in its free and H3K36me3 nucleosome-bound states. We demonstrated a unique architecture of Rpd3S, in which two copies of Eaf3-Rco1 heterodimers are asymmetrically assembled with Rpd3 and Sin3 to form a catalytic core complex. Multivalent recognition of two H3K36me3 marks, nucleosomal DNA and linker DNAs by Eaf3, Sin3 and Rco1 positions the catalytic centre of Rpd3 next to the histone H4 N-terminal tail for deacetylation. In an alternative catalytic mode, combinatorial readout of unmethylated histone H3 lysine 4 and H3K36me3 by Rco1 and Eaf3 directs histone H3-specific deacetylation except for the registered histone H3 acetylated lysine 9. Collectively, our work illustrates dynamic and diverse modes of multivalent nucleosomal engagement and methylation-guided deacetylation by Rpd3S, highlighting the exquisite complexity of epigenetic regulation with delicately designed multi-subunit enzymatic machineries in transcription and beyond. |
External links | Nature / PubMed:37468628 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.7 - 3.96 Å |
Structure data | EMDB-33845: Cryo-EM map of Rpd3S complex EMDB-33846: Cryo-EM map of Rpd3S:head-bridge-right arm EMDB-33847: Cryo-EM map of Rpd3S:bridge-left arm EMDB-33848: Cryo-EM map of Eaf3 CHD bound to H3K36me3 nucleosome EMDB-33849: Cryo-EM map of Rpd3S in loose-state Rpd3S-NCP complex EMDB-33850: Cryo-EM map of Rpd3S in close-state Rpd3S-NCP complex EMDB-33851: Cryo-EM map of Rpd3S complex bound to H3K36me3 nucleosome in close state EMDB-33852: Cryo-EM msp of Rpd3S complex bound to H3K36me3 nucleosome in loose state |
Chemicals | ChemComp-ZN: |
Source |
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Keywords | GENE REGULATION / Dynamic Histone Modifications / Histone Deacetylase Complex |