Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes

Chhabi K. Govind, Hongfang Qiu, Daniel S. Ginsburg, Chun Ruan, Kimberly Hofmeyer, Cuihua Hu, Venkatesh Swaminathan, Jerry L. Workman, Bing Li, Alan G. Hinnebusch

Research output: Contribution to journalArticle

146 Scopus citations

Abstract

Methylation of histone H3 by Set1 and Set2 is required for deacetylation of nucleosomes in coding regions by histone deacetylase complexes (HDACs) Set3C and Rpd3C(S), respectively. We report that Set3C and Rpd3C(S) are cotranscriptionally recruited in the absence of Set1 and Set2, but in a manner stimulated by Pol II CTD kinase Cdk7/Kin28. Consistently, Rpd3C(S) and Set3C interact with Ser5-phosphorylated Pol II and histones in extracts, but only the histone interactions require H3 methylation. Moreover, reconstituted Rpd3C(S) binds specifically to Ser5-phosphorylated CTD peptides in vitro. Hence, whereas interaction with methylated H3 residues is required for Rpd3C(S) and Set3C deacetylation activities, their cotranscriptional recruitment is stimulated by the phosphorylated CTD. We further demonstrate that Rpd3, Hos2, and Hda1 have overlapping functions in deacetylating histones and suppressing cotranscriptional histone eviction. A strong correlation between increased acetylation and lower histone occupancy in HDA mutants implies that histone acetylation is important for nucleosome eviction.

Original languageEnglish (US)
Pages (from-to)234-246
Number of pages13
JournalMolecular cell
Volume39
Issue number2
DOIs
StatePublished - Jul 1 2010

Keywords

  • DNA
  • Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Govind, C. K., Qiu, H., Ginsburg, D. S., Ruan, C., Hofmeyer, K., Hu, C., Swaminathan, V., Workman, J. L., Li, B., & Hinnebusch, A. G. (2010). Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes. Molecular cell, 39(2), 234-246. https://doi.org/10.1016/j.molcel.2010.07.003