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

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...

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Published inMolecular cell Vol. 52; no. 3; pp. 314 - 324
Main Authors Schröder, Sebastian, Herker, Eva, Itzen, Friederike, He, Daniel, Thomas, Sean, Gilchrist, Daniel A, Kaehlcke, Katrin, Cho, Sungyoo, Pollard, Katherine S, Capra, John A, Schnölzer, Martina, Cole, Philip A, Geyer, Matthias, Bruneau, Benoit G, Adelman, Karen, Ott, Melanie
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 07.11.2013
Subjects
Acetylation
Animals
DNA-directed RNA polymerase
Early Growth Response Protein 2 - biosynthesis
Embryonic Stem Cells - cytology
essential genes
Gene Expression Regulation
Genes, fos - genetics
histones
Histones - genetics
Histones - metabolism
Humans
lysine
Lysine - genetics
mammals
mutation
p300-CBP Transcription Factors - genetics
p300-CBP Transcription Factors - metabolism
Promoter Regions, Genetic
RNA Polymerase II - genetics
RNA Polymerase II - metabolism
transcription (genetics)
transcription factors
Transcription, Genetic
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Summary: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.
Bibliography:http://dx.doi.org/10.1016/j.molcel.2013.10.009
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Present address: Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2013.10.009