title: Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells.
abstract: Lysine acetylation regulates transcription by targeting histones and nonhistone proteins. Here we report that the central regulator of transcription, RNA polymerase II, is subject to acetylation in mammalian cells. Acetylation occurs at eight lysines within the C-terminal domain (CTD) of the largest polymerase subunit and is mediated by p300/KAT3B. CTD acetylation is specifically enriched downstream of the transcription start sites of polymerase-occupied genes genome-wide, indicating a role in early stages of transcription initiation or elongation. Mutation of lysines or p300 inhibitor treatment causes the loss of epidermal growth-factor-induced expression of c-Fos and Egr2, immediate-early genes with promoter-proximally paused polymerases, but does not affect expression or polymerase occupancy at housekeeping genes. Our studies identify acetylation as a new modification of the mammalian RNA polymerase II required for the induction of growth factor response genes.
authors.affiliation: Gladstone Institutes, San Francisco, CA 94158, USA; University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schröder
authors.forename: Eva
authors.initials: E
authors.lastname: Herker
authors.forename: Friederike
authors.initials: F
authors.lastname: Itzen
authors.forename: Daniel
authors.initials: D
authors.lastname: He
authors.forename: Sean
authors.initials: S
authors.lastname: Thomas
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Gilchrist
authors.forename: Katrin
authors.initials: K
authors.lastname: Kaehlcke
authors.forename: Sungyoo
authors.initials: S
authors.lastname: Cho
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Pollard
authors.forename: John A
authors.initials: JA
authors.lastname: Capra
authors.forename: Martina
authors.initials: M
authors.lastname: Schnölzer
authors.forename: Philip A
authors.initials: PA
authors.lastname: Cole
authors.forename: Matthias
authors.initials: M
authors.lastname: Geyer
authors.forename: Benoit G
authors.initials: BG
authors.lastname: Bruneau
authors.forename: Karen
authors.initials: K
authors.lastname: Adelman
authors.forename: Melanie
authors.initials: M
authors.lastname: Ott
mesh_terms: D000107:Acetylation; D000818:Animals; D051767:Early Growth Response Protein 2 / Q000096:biosynthesis; D053595:Embryonic Stem Cells / Q000166:cytology; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics; D006657:Histones / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D006657:Histones; D050880:p300-CBP Transcription Factors; D012319:RNA Polymerase II; D008239:Lysine