title: The Bur1/Bur2 complex is required for histone H2B monoubiquitination by Rad6/Bre1 and histone methylation by COMPASS.
abstract: To date, several classes of enzymes have been shown to affect transcription by catalyzing the modifications of nucleosomes via methylation. Employing our global proteomic screen, GPS, we have determined that the loss of Bur2, a component of the Bur1/Bur2 cyclin-dependent protein kinase, results in a decrease in histone H3(K4) methylation catalyzed by COMPASS. Furthermore, Bur1/Bur2 is required for histone H2B monoubiquitination by Rad6/Bre1. The effect on histone monoubiquitination and methylation is the result of defective Bur1/Bur2-mediated phosphorylation of Rad6 on its serine residue 120 and proper recruitment of the Paf1 complex to chromatin. We have also demonstrated that serine 120 of Rad6 is required for histone H2B monoubiquitination and the regulation of gene expression in vivo. Our results identify in vivo substrates for Bur1/Bur2, thus linking its role to transcriptional elongation and demonstrating a potential activation mechanism for histone H2B monoubiquitination by the Rad6/Bre1 complex.
authors.affiliation: Department of Biochemistry, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, Missouri 63104, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Wood
authors.forename: Jessica
authors.initials: J
authors.lastname: Schneider
authors.forename: Jim
authors.initials: J
authors.lastname: Dover
authors.forename: Mark
authors.initials: M
authors.lastname: Johnston
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D000595:Amino Acid Sequence; D018844:Cyclin-Dependent Kinases / Q000502:physiology*; D016213:Cyclins / Q000502:physiology*; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D010766:Phosphorylation; D011496:Protein Methyltransferases; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology*; D012694:Serine / Q000502:physiology; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000502:physiology*
chemical_list: C472168:Bre1 protein, S cerevisiae; C414164:Bur2 protein, S cerevisiae; D016213:Cyclins; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D025801:Ubiquitin; D012694:Serine; D000076983:Histone Methyltransferases; D011496:Protein Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D018844:Cyclin-Dependent Kinases; C414163:SGV1 protein, S cerevisiae