Acetylation of RNA polymerase II regulates growth-factor-induced gene transcription in mammalian cells.

Schröder S, Herker E, Itzen F, He D, Thomas S, Gilchrist DA, Kaehlcke K, Cho S, Pollard KS, Capra JA, Schnölzer M, Cole PA, Geyer M, Bruneau BG, Adelman K, Ott M
Mol Cell. 2013 52 (3): 314-24

PMID: 24207025 · PMCID: PMC3936344 · DOI:10.1016/j.molcel.2013.10.009

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.

Copyright © 2013 Elsevier Inc. All rights reserved.

MeSH Terms (13)

Acetylation Animals Early Growth Response Protein 2 Embryonic Stem Cells Gene Expression Regulation Genes, fos Histones Humans Lysine p300-CBP Transcription Factors Promoter Regions, Genetic RNA Polymerase II Transcription, Genetic

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