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Genes Dev. 2014 Sep 15;28(18):1983-8. doi: 10.1101/gad.247940.114. Epub 2014 Aug 28.

Nascent RNA interaction keeps PRC2 activity poised and in check.

Author information

1
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York 10016, USA;
2
Department of Cell and Developmental Biology, Epigenetics Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
3
Center for Health Informatics and Bioinformatics, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, 10016, USA.

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 stem cells. 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.

KEYWORDS:

EZH2; JARID2; PRC2; chromatin; ncRNA

PMID:
25170018
PMCID:
PMC4173153
DOI:
10.1101/gad.247940.114
[Indexed for MEDLINE]
Free PMC Article

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