Nascent RNA interaction keeps PRC2 activity poised and in check

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

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

Polycomb-repressive complex 2 (PRC2) facilitates the maintenance and inheritance of chromatin domains repressive to transcription through catalysis of methylation of histone H3 at Lys27 (H3K27me2/3). However, through its EZH2 subunit, PRC2 also binds to nascent transcripts from active genes that are devoid of H3K27me2/3 in embryonic stemcells. Here, biochemical analyses indicated that RNA interaction inhibits SET domain-containing proteins, such as PRC2, nonspecifically in vitro. However, CRISPR-mediated truncation of a PRC2-interacting nascent RNA rescued PRC2-mediated deposition of H3K27me2/3. That PRC2 activity is inhibited by interactions with nascent transcripts supports a model in which PRC2 can only mark for repression those genes silenced by transcriptional repressors.

Original languageEnglish (US)
Pages (from-to)1983-1988
Number of pages6
JournalGenes and Development
Volume28
Issue number18
DOIs
StatePublished - Sep 15 2014
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014 Kaneko et al.

Keywords

  • Chromatin
  • EZH2
  • JARID2
  • PRC2
  • ncRNA

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