title: Site-specific methylation and acetylation of lysine residues in the C-terminal domain (CTD) of RNA polymerase II.
abstract: Dynamic modification of heptad-repeats with the consensus sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7 of RNA polymerase II (RNAPII) C-terminal domain (CTD) regulates transcription-coupled processes. Mass spectrometry analysis revealed that K7-residues in non-consensus repeats of human RNAPII are modified by acetylation, or mono-, di-, and tri-methylation. K7ac, K7me2, and K7me3 were found exclusively associated with phosphorylated CTD peptides, while K7me1 occurred also in non-phosphorylated CTD. The monoclonal antibody 1F5 recognizes K7me1/2 residues in CTD and reacts with RNAPIIA. Treatment of cellular extracts with phosphatase or of cells with the kinase inhibitor flavopiridol unmasked the K7me1/2 epitope in RNAPII0, consistent with the association of K7me1/2 marks with phosphorylated CTD peptides. Genome-wide profiling revealed high levels of K7me1/2 marks at the transcriptional start site of genes for sense and antisense transcribing RNAPII. The new K7 modifications further expand the mammalian CTD code to allow regulation of differential gene expression.
authors.affiliation: a Department of Molecular Epigenetics; Helmholtz Center Munich; Center for Integrated Protein Science Munich ; Munich , Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Voss
authors.affiliation: b Biomedical Center Munich; Ludwig Maximilians University Munich ; Planegg-Martinsried , Germany.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Forné
authors.affiliation: c Centre d'Immunologie de Marseille-Luminy; Université Aix-Marseille; Campus de Luminy , France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Descostes
authors.affiliation: a Department of Molecular Epigenetics; Helmholtz Center Munich; Center for Integrated Protein Science Munich ; Munich , Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Hintermair
authors.affiliation: a Department of Molecular Epigenetics; Helmholtz Center Munich; Center for Integrated Protein Science Munich ; Munich , Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schüller
authors.affiliation: d Institute of Molecular Genetics of Montpellier (IGMM); UMR5535 CNRS ; Montpellier , France.
authors.forename: Muhammad Ahmad
authors.initials: MA
authors.lastname: Maqbool
authors.affiliation: a Department of Molecular Epigenetics; Helmholtz Center Munich; Center for Integrated Protein Science Munich ; Munich , Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Heidemann
authors.affiliation: e Institute of Molecular Immunology; Helmholtz Center Munich ; Munich , Germany.
authors.forename: Andrew
authors.initials: A
authors.lastname: Flatley
authors.affiliation: c Centre d'Immunologie de Marseille-Luminy; Université Aix-Marseille; Campus de Luminy , France.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.affiliation: f Centre Nacional D'Anàlisi Genòmica; Parc Cientific de Barcelona ; Barcelona , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Gut
authors.affiliation: f Centre Nacional D'Anàlisi Genòmica; Parc Cientific de Barcelona ; Barcelona , Spain.
authors.forename: Ivo
authors.initials: I
authors.lastname: Gut
authors.affiliation: e Institute of Molecular Immunology; Helmholtz Center Munich ; Munich , Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Kremmer
authors.affiliation: d Institute of Molecular Genetics of Montpellier (IGMM); UMR5535 CNRS ; Montpellier , France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Andrau
authors.affiliation: a Department of Molecular Epigenetics; Helmholtz Center Munich; Center for Integrated Protein Science Munich ; Munich , Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
mesh_terms: D000107:Acetylation; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012319:RNA Polymerase II / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D061785:Transcription Initiation, Genetic
chemical_list: D000911:Antibodies, Monoclonal; D012319:RNA Polymerase II; D008239:Lysine
keywords: C-terminal domain (CTD); CTD code; RNA polymerase II; lysine methylation