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PMID: 24141703 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.

Nature structural & molecular biology ·Vol. 20 ·No. 11 ·2013-11-00 ·Pages 1258-64

Kaneko S, Son J, Shen SS, Reinberg D, Bonasio R

Abstract

EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27me3 marks is well understood, but how it is regulated and directed to specific genes before and during differentiation remains unknown. Here, we report that PRC2 binds at low levels to a majority of promoters in mouse ESCs, including many that are active and devoid of H3K27me3. Using in vivo RNA-protein cross-linking, we show that EZH2 directly binds the 5' region of nascent RNAs transcribed from a subset of these promoters and that these binding events correlate with decreased H3K27me3. Our findings suggest a molecular mechanism by which PRC2 senses the transcriptional state of the cell and translates it into epigenetic information.

MeSH Terms
Animals Embryonic Stem Cells/metabolism Gene Expression Profiling Mice Models, Biological Polycomb Repressive Complex 2/metabolism Promoter Regions, Genetic Protein Binding RNA, Messenger/metabolism
Chemicals
RNA, Messenger Polycomb Repressive Complex 2
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kaneko Syuzo
1] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York, USA. [2] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York, USA.
Son Jinsook
Shen Steven S
Reinberg Danny
Bonasio Roberto
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.2700
Published
2013-11-00
Epub
2013-00-20
Pages
1258-64
Language
English
Region
United States
NLM ID
101186374
PMCID
PMC3839660
Subset
IM
Grants
NCI NIH HHS · P30 CA016087 · United States
NIGMS NIH HHS · GM-64844 · United States
PHS HHS · R37-37120 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM064844 · United States
Databases
GEO
GSE49435
Corrections
CommentIn
PMID: 24304912
External Links
PubMed source DOI: 10.1038/nsmb.2700 PMC Full Text View journal details
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