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TitleStructural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex.
Journal, issue, pagesCell Res, Vol. 33, Issue 10, Page 790-801, Year 2023
Publish dateSep 4, 2023
AuthorsShuqi Dong / Huadong Li / Meilin Wang / Nadia Rasheed / Binqian Zou / Xijie Gao / Jiali Guan / Weijie Li / Jiale Zhang / Chi Wang / Ningkun Zhou / Xue Shi / Mei Li / Min Zhou / Junfeng Huang / He Li / Ying Zhang / Koon Ho Wong / Xiaofei Zhang / William Chong Hang Chao / Jun He /
PubMed AbstractIn Saccharomyces cerevisiae, cryptic transcription at the coding region is prevented by the activity of Sin3 histone deacetylase (HDAC) complex Rpd3S, which is carried by the transcribing RNA ...In Saccharomyces cerevisiae, cryptic transcription at the coding region is prevented by the activity of Sin3 histone deacetylase (HDAC) complex Rpd3S, which is carried by the transcribing RNA polymerase II (RNAPII) to deacetylate and stabilize chromatin. Despite its fundamental importance, the mechanisms by which Rpd3S deacetylates nucleosomes and regulates chromatin dynamics remain elusive. Here, we determined several cryo-EM structures of Rpd3S in complex with nucleosome core particles (NCPs), including the H3/H4 deacetylation states, the alternative deacetylation state, the linker tightening state, and a state in which Rpd3S co-exists with the Hho1 linker histone on NCP. These structures suggest that Rpd3S utilizes a conserved Sin3 basic surface to navigate through the nucleosomal DNA, guided by its interactions with H3K36 methylation and the extra-nucleosomal DNA linkers, to target acetylated H3K9 and sample other histone tails. Furthermore, our structures illustrate that Rpd3S reconfigures the DNA linkers and acts in concert with Hho1 to engage the NCP, potentially unraveling how Rpd3S and Hho1 work in tandem for gene silencing.
External linksCell Res / PubMed:37666978 / PubMed Central
MethodsEM (single particle)
Resolution2.9 - 3.46 Å
Structure data

EMDB-37096, PDB-8kc7:
Rpd3S histone deacetylase complex
Method: EM (single particle) / Resolution: 3.46 Å

EMDB-37122, PDB-8kd2:
Rpd3S in complex with 187bp nucleosome
Method: EM (single particle) / Resolution: 3.02 Å

EMDB-37123, PDB-8kd3:
Rpd3S in complex with nucleosome with H3K36MLA modification, H3K9Q mutation and 187bp DNA
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-37124, PDB-8kd4:
Rpd3S in complex with nucleosome with H3K36MLA modification and 187bp DNA, class1
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-37125, PDB-8kd5:
Rpd3S in complex with nucleosome with H3K36MLA modification and 187bp DNA, class2
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-37126, PDB-8kd6:
Rpd3S in complex with nucleosome with H3K36MLA modification and 187bp DNA, class3
Method: EM (single particle) / Resolution: 3.07 Å

EMDB-37127, PDB-8kd7:
Rpd3S in complex with nucleosome with H3K36MLA modification and 167bp DNA
Method: EM (single particle) / Resolution: 3.09 Å

Chemicals

ChemComp-ZN:
Unknown entry

Source
  • saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
  • saccharomyces cerevisiae (brewer's yeast)
  • xenopus laevis (African clawed frog)
  • synthetic construct (others)
KeywordsTRANSCRIPTION / Rpd3S / HDAC / Hho1 / cryptic transcription

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