title: The RNA polymerase II kinase Ctk1 regulates positioning of a 5' histone methylation boundary along genes.
abstract: In yeast and other eukaryotes, the histone methyltransferase Set1 mediates methylation of lysine 4 on histone H3 (H3K4me). This modification marks the 5' end of transcribed genes in a 5'-to-3' tri- to di- to monomethyl gradient and promotes association of chromatin-remodeling and histone-modifying enzymes. Here we show that Ctk1, the serine 2 C-terminal domain (CTD) kinase for RNA polymerase II (RNAP II), regulates H3K4 methylation. We found that CTK1 deletion nearly abolished H3K4 monomethylation yet caused a significant increase in H3K4 di- and trimethylation. Both in individual genes and genome-wide, loss of CTK1 disrupted the H3K4 methylation patterns normally observed. H3K4me2 and H3K4me3 spread 3' into the bodies of genes, while H3K4 monomethylation was diminished. These effects were dependent on the catalytic activity of Ctk1 but are independent of Set2-mediated H3K36 methylation. Furthermore, these effects are not due to spurious transcription initiation in the bodies of genes, to changes in RNAP II occupancy, to changes in serine 5 CTD phosphorylation patterns, or to "transcriptional stress." These data show that Ctk1 acts to restrict the spread of H3K4 methylation through a mechanism that is independent of a general transcription defect. The evidence presented suggests that Ctk1 controls the maintenance of suppressive chromatin in the coding regions of genes by both promoting H3K36 methylation, which leads to histone deacetylation, and preventing the 3' spread of H3K4 trimethylation, a mark associated with transcriptional initiation.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, 405 Mary Ellen Jones, Chapel Hill, NC 27599-7260, USA.
authors.forename: Tiaojiang
authors.initials: T
authors.lastname: Xiao
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Bhargavi
authors.initials: B
authors.lastname: Rao
authors.forename: R Nicholas
authors.initials: RN
authors.lastname: Laribee
authors.forename: Rose
authors.initials: R
authors.lastname: O'Rourke
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Buck
authors.forename: Jack F
authors.initials: JF
authors.lastname: Greenblatt
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.forename: Jason D
authors.initials: JD
authors.lastname: Lieb
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
mesh_terms: D024506:5' Flanking Region; D002843:Chromatin / Q000378:metabolism; D005800:Genes, Fungal; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: C118305:CTDK-I protein complex, S cerevisiae; D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D008780:Methyltransferases; C448996:Set2 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D011494:Protein Kinases; D012319:RNA Polymerase II; D008239:Lysine