7yi3 › Citations

Diverse modes of H3K36me3-guided nucleosomal deacetylation by Rpd3S.

<div class='caption-title'>Cryo-EM structure of Rpd3S complex and interactions among subunits.</div>
<div class='caption-title'>Cryo-EM structure of Rpd3S complex bound to H3K36me3 nucleosome.</div>
<div class='caption-title'>Details of the interface between the Rpd3S complex and the H3K36me3 nucleosome.</div>
Guan H, Wang P, Zhang P, Ruan C, Ou Y, Peng B, Zheng X, Lei J, Li B, Yan C, Li H
OpenAccess logo Nature (2023)
Related entries: 7yi0, 7yi1, 7yi2, 7yi4, 7yi5

Cited: 4 times
EuropePMC logo PMID: 37468628

Abstract

Context-dependent dynamic histone modifications constitute a key epigenetic mechanism in gene regulation1-4. The Rpd3 small (Rpd3S) complex recognizes histone H3 trimethylation on lysine 36 (H3K36me3) and deacetylates histones H3 and H4 at multiple sites across transcribed regions5-7. 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.

Articles citing this publication (4)

  1. Structural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex. Dong S, Li H, Wang M, Rasheed N, Zou B, Gao X, Guan J, Li W, Zhang J, Wang C, Zhou N, Shi X, Li M, Zhou M, Huang J, Li H, Zhang Y, Wong KH, Zhang X, Chao WCH, He J. Cell Res 33 790-801 (2023)
  2. Rpd3S meets the nucleosome. Carrozza MJ, Workman JL. Cell Res (2023)
  3. Letter Structural basis for nucleosome binding and catalysis by the yeast Rpd3S/HDAC holoenzyme. Zhang Y, Xu M, Wang P, Zhou J, Wang G, Han S, Cai G, Wang X. Cell Res (2023)
  4. Structure of the complete Saccharomyces cerevisiae Rpd3S-nucleosome complex. Markert JW, Vos SM, Farnung L. Nat Commun 14 8128 (2023)


Quick links