title: Phosphorylated Pol II CTD recruits multiple HDACs, including Rpd3C(S), for methylation-dependent deacetylation of ORF nucleosomes.
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.
authors.affiliation: Laboratory of Gene Regulation and Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA. govind@oakland.edu
authors.forename: Chhabi K
authors.initials: CK
authors.lastname: Govind
authors.forename: Hongfang
authors.initials: H
authors.lastname: Qiu
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Ginsburg
authors.forename: Chun
authors.initials: C
authors.lastname: Ruan
authors.forename: Kimberly
authors.initials: K
authors.lastname: Hofmeyer
authors.forename: Cuihua
authors.initials: C
authors.lastname: Hu
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Swaminathan
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Workman
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Alan G
authors.initials: AG
authors.lastname: Hinnebusch
mesh_terms: D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D016366:Open Reading Frames / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; C411250:SET1 protein, S cerevisiae; D018844:Cyclin-Dependent Kinases; C084210:Kin28 protein kinase, S cerevisiae; D012319:RNA Polymerase II; C499673:HDA1 protein, S cerevisiae; C519410:HOS2 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; C511735:Set3 protein, S cerevisiae; D006655:Histone Deacetylases