Phosphorylated Pol II CTD Recruits Multiple HDACs, Including Rpd3C(S), for Methylation-Dependent Deacetylation of ORF Nucleosomes

• Published in: Molecular cell Vol. 39; no. 2; pp. 234 - 246
• Main Authors: Govind, Chhabi K., Qiu, Hongfang, Ginsburg, Daniel S., Ruan, Chun, Hofmeyer, Kimberly, Hu, Cuihua, Swaminathan, Venkatesh, Workman, Jerry L., Li, Bing, Hinnebusch, Alan G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.07.2010
• Subjects: Cyclin-Dependent Kinases - genetics; Cyclin-Dependent Kinases - metabolism; DNA; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histones - genetics; Histones - metabolism; Methylation; Methyltransferases - genetics; Methyltransferases - metabolism; Nucleosomes - genetics; Nucleosomes - metabolism; Open Reading Frames - physiology; Phosphorylation - physiology; PROTEINS; RNA Polymerase II - genetics; RNA Polymerase II - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; PROTEINS; DNA
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/j.molcel.2010.07.003

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. ► HDAs Rpd3C(S), Set3C, and Hda1 are recruited by Gcn4 to the induced ARG1 ORF ► HDAs act redundantly to suppress cotranscriptional histone eviction from the ORF ► Recruitment of Rpd3C(S) and Set3C is enhanced by Pol II CTD phosphorylation ► Binding of Rpd3C(S) to methylated H3 is facilitated by CTD-Rpd3C(S) interaction