Nascent RNA interaction keeps PRC2 activity poised and in check
- 1Howard Hughes Medical Institute,
- 2Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York 10016, USA;
- 3Department of Cell and Developmental Biology, Epigenetics Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
- 4Center for Health Informatics and Bioinformatics, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, 10016, USA
- Corresponding author: danny.reinberg{at}nyumc.org
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↵5 These authors contributed equally to this work.
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.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.247940.114.
- Received June 25, 2014.
- Accepted August 13, 2014.
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