Volume 33, No 12, Dec 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 12, December 2023: 971-974   |  Open Access

LETTERS TO THE EDITOR

Structural basis for nucleosome binding and catalysis by the yeast Rpd3S/HDAC holoenzyme

Yueyue Zhang^1,† , Mengxue Xu^1,† , Po Wang¹ , Jiahui Zhou¹ , Guangxian Wang¹ , Shuailong Han¹ , Gang Cai^1,2,* , Xuejuan Wang^1,2,*

¹The First Affiliated Hospital of USTC, MOE Key Laboratory for Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
²Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases, Hefei, Anhui, China
^†These authors contributed equally: Yueyue Zhang, Mengxue Xu
Correspondence: Gang Cai(gcai@ustc.edu.cn)Xuejuan Wang(xuejuan@ustc.edu.cn)

Dear Editor,

Histone deacetylases (HDACs) are evolutionally conserved enzymes that remove acetyl modifications from histones and play a central role in epigenetic gene silencing.1 Class I HDACs are promising targets for epigenetic therapies for a range of diseases such as cancers, inflammations, infections, and neurological diseases.2 Yeast Rpd3 is the founding member of class I HDACs, which forms two distinct complexes: the ∼1.2 MDa Rpd3L deacetylating histones at promoter regions, and the ∼0.6 MDa Rpd3S targeting transcribed regions to suppress intragenic transcription initiation.3,4 Rpd3S consists of three core proteins: Rpd3, Sin3, and Ume15 along with two dedicated chromatin binding subunits: Eaf3 and Rco1.6 The structures of the yeast Rpd3S complex and its human homolog Sin3B complex have been recently reported.7,8 Here, we report the cryo-electron microscopy (cryo-EM) structure of the Rpd3S holoenzyme binding a nucleosome at 3.7 Å resolution (Supplementary information, Table S1). The structure illuminates an intact H3 tail (1–24 aa) binding to the Rpd3S complex in a catalysis-competent conformation, with the H3K18 residue poised for catalysis.

https://doi.org/10.1038/s41422-023-00884-2

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