Acetylation of RNA Polymerase II Regulates Growth-Factor-Induced Gene Transcription in Mammalian Cells

Sebastian Schröder, Eva Herker, Friederike Itzen, Daniel He, Sean Thomas, Daniel A. Gilchrist, Katrin Kaehlcke, Sungyoo Cho, Katherine S. Pollard, John A. Capra, Martina Schnölzer, Philip A. Cole, Matthias Geyer, Benoit G. Bruneau, Karen Adelman, Melanie Ott

Research output: Contribution to journalArticlepeer-review

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 oflysines 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.

Original languageEnglish (US)
Pages (from-to)314-324
Number of pages11
JournalMolecular cell
Volume52
Issue number3
DOIs
StatePublished - Nov 7 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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