title: Methylation of RNA polymerase II non-consensus Lysine residues marks early transcription in mammalian cells.
abstract: Dynamic post-translational modification of RNA polymerase II (RNAPII) coordinates the co-transcriptional recruitment of enzymatic complexes that regulate chromatin states and processing of nascent RNA. Extensive phosphorylation of serine residues at the largest RNAPII subunit occurs at its structurally-disordered C-terminal domain (CTD), which is composed of multiple heptapeptide repeats with consensus sequence Y1-S2-P3-T4-S5-P6-S7. Serine-5 and Serine-7 phosphorylation mark transcription initiation, whereas Serine-2 phosphorylation coincides with productive elongation. In vertebrates, the CTD has eight non-canonical substitutions of Serine-7 into Lysine-7, which can be acetylated (K7ac). Here, we describe mono- and di-methylation of CTD Lysine-7 residues (K7me1 and K7me2). K7me1 and K7me2 are observed during the earliest transcription stages and precede or accompany Serine-5 and Serine-7 phosphorylation. In contrast, K7ac is associated with RNAPII elongation, Serine-2 phosphorylation and mRNA expression. We identify an unexpected balance between RNAPII K7 methylation and acetylation at gene promoters, which fine-tunes gene expression levels.
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.|Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.|Graduate Program in Areas of Basic and Applied Biology, University of Porto, Porto, Portugal.
authors.forename: João D
authors.initials: JD
authors.lastname: Dias
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.
authors.forename: Tiago
authors.initials: T
authors.lastname: Rito
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Torlai Triglia
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kukalev
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.|Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Ferrai
authors.affiliation: Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Mita
authors.initials: M
authors.lastname: Chotalia
authors.affiliation: Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Emily
authors.initials: E
authors.lastname: Brookes
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Epigenetic Regulation and Chromatin Architecture Group, Berlin Institute for Medical Systems Biology, Max-Delbrück Centre for Molecular Medicine, Berlin, Germany.|Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom.
authors.forename: Ana
authors.identifier: http://orcid.org/0000-0002-7493-6288
authors.initials: A
authors.lastname: Pombo
mesh_terms: D000818:Animals; D032921:Consensus; D005786:Gene Expression Regulation; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D012694:Serine; D012319:RNA Polymerase II; D008239:Lysine
keywords: C-terminal domain; RNA polymerase II; chromosomes; computational biology; genes; methylation; mouse; non-histone protein lysine methylation; post-transcriptional modification; systems biology; transcription cycle