title: Ctk complex-mediated regulation of histone methylation by COMPASS.
abstract: A comparative global proteomic screen identified factors required for COMPASS (complex of proteins associated with Set1)-mediated mono-, di-, and trimethylation of the fourth lysine of histone H3 (H3K4), which included components of a cyclin-dependent protein kinase (Ctk complex) that phosphorylates the C-terminal domain of the largest subunit of RNA polymerase II (Pol II). Our results indicate that histone H3K4 methylation levels are regulated by the Ctk1, Ctk2, and Ctk3 components of the Ctk complex. We show that loss of Ctk1 kinase activity results in reduced histone H3K4 monomethylation levels, followed by a global increase in histone H3K4 trimethylation levels on chromatin. Ctk1 loss does not appear to have a substantial effect on histone H2B monoubiquitination levels or COMPASS and Paf1 complex phosphorylation. Our chromatin immunoprecipitation studies demonstrate that histone H3 eviction during active transcription is decelerated in a CTK1 deletion strain in response to reduced levels of Pol II recruitment. Our in vitro studies show that the onset of monomethylation on an unmethylated histone H3 by COMPASS is virtually immediate, while the onset of trimethylation occurs upon extended time of association between the histone tail and COMPASS. Our study suggests a role for the Ctk complex in the regulation of the pattern of H3K4 mono-, di-, and trimethylation via COMPASS.
authors.affiliation: Saint Louis University School of Medicine, Department of Biochemistry, 1402 South Grand Blvd., St. Louis, MO 63104, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Wood
authors.forename: Abhijit
authors.initials: A
authors.lastname: Shukla
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneider
authors.forename: Jung Shin
authors.initials: JS
authors.lastname: Lee
authors.forename: Julie D
authors.initials: JD
authors.lastname: Stanton
authors.forename: Tiffany
authors.initials: T
authors.lastname: Dzuiba
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: John
authors.initials: J
authors.lastname: Wyrick
authors.forename: Sukesh R
authors.initials: SR
authors.lastname: Bhaumik
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D047369:Chromatin Immunoprecipitation; D018844:Cyclin-Dependent Kinases / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C118305:CTDK-I protein complex, S cerevisiae; D006657:Histones; D020543:Proteome; D029701:Saccharomyces cerevisiae Proteins; D011495:Histone-Lysine N-Methyltransferase; D011494:Protein Kinases; D018844:Cyclin-Dependent Kinases; D004257:DNA Polymerase II; D008239:Lysine