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PMID: 18541663 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Roles for Ctk1 and Spt6 in regulating the different methylation states of histone H3 lysine 36.

Molecular and cellular biology ·Vol. 28 ·No. 16 ·2008-08-00 ·Pages 4915-26

Youdell ML, Kizer KO, Kisseleva-Romanova E, Fuchs SM, Duro E, Strahl BD, Mellor J

Abstract

Set2 (KMT3)-dependent methylation (me) of histone H3 at lysine 36 (H3K36) promotes deacetylation of transcribed chromatin and represses cryptic promoters within genes. Although Set2 is the only methyltransferase (KMTase) for H3K36 in yeast, it is not known if Set2 is regulated or whether the different methylation states at H3K36 are functionally distinct. Here we show that the N-terminal 261 residues of Set2 (Set2(1-261)), containing the SET KMTase domain, are sufficient for H3K36me2, histone deacetylation, and repression of cryptic promoters at STE11. Set2-catalyzed H3K36me2 does not require either Ctk1-dependent phosphorylation of RNA polymerase II (RNAPII) or the presence of the phospho-C-terminal domain (CTD) interaction (SRI) domain of Set2. This finding is consistent with a known correlation between H3K36me2 and whether a gene is on or off, but not the level of activity of a gene. By contrast, H3K36me3 requires Spt6, proline 38 on histone H3 (H3P38), the CTD of RNAPII, Ctk1, and the C-terminal SRI domain of Set2. We suggest that the C-terminal region of Set2, in conjunction with the phosphorylated CTD of RNAPII, influences the KMTase activity to promote H3K36me3 during transcription elongation.

MeSH Terms
Acetylation Chromatin/metabolism Gene Expression Regulation, Fungal Histone Chaperones Histones/metabolism Lysine/metabolism Methylation Nuclear Proteins/chemistry,metabolism Promoter Regions, Genetic/genetics Protein Kinases/metabolism Protein Structure, Tertiary RNA Polymerase II/chemistry,metabolism Recombinant Proteins/metabolism Repressor Proteins/metabolism Saccharomyces cerevisiae/enzymology,genetics Saccharomyces cerevisiae Proteins/chemistry,genetics,metabolism Transcriptional Elongation Factors
Chemicals
CTDK-I protein complex, S cerevisiae Chromatin Histone Chaperones Histones Nuclear Proteins Recombinant Proteins Repressor Proteins SPT6 protein, S cerevisiae Saccharomyces cerevisiae Proteins Transcriptional Elongation Factors Protein Kinases RNA Polymerase II Lysine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Youdell Michael L
Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Kizer Kelby O
Kisseleva-Romanova Elena
Fuchs Stephen M
Duro Eris
Strahl Brian D
Mellor Jane
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.00001-08
Published
2008-08-00
Epub
2008-00-09
Pages
4915-26
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2519698
Subset
IM
Grants
Wellcome Trust · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
NIGMS NIH HHS · F32 GM080896-02 · United States
NIGMS NIH HHS · F32 GM080896 · United States
NIGMS NIH HHS · F32 GM080896-01 · United States
Cancer Research UK · United Kingdom
External Links
PubMed source DOI: 10.1128/MCB.00001-08 PMC Full Text View journal details
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