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

Syuzo Kaneko, Jinsook Son, Steven S. Shen, Danny Reinberg, Roberto Bonasio

Research output: Contribution to journalArticlepeer-review

239 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1258-1264
Number of pages7
JournalNature Structural and Molecular Biology
Volume20
Issue number11
DOIs
StatePublished - Nov 2013

Bibliographical note

Funding Information:
We thank W.W. Tee, L. Vales and P. Voigt for their critical assessment of the manuscript, T. Cech (University of Colorado Boulder) for discussions and the Genome Technology Center at New York University for help with sequencing. This work was supported by grants from the US National Institutes of Health (GM-64844 and R37-37120 to D.R.) and the Howard Hughes Medical Institute (to D.R.). R.B. was supported by a Helen Hay Whitney Foundation postdoctoral fellowship and by the Helen L. and Martin S. Kimmel Center for Stem Cell Biology postdoctoral fellow award.

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