title: Nascent RNA interaction keeps PRC2 activity poised and in check.
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.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York 10016, USA;
authors.forename: Syuzo
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York 10016, USA;
authors.forename: Jinsook
authors.initials: J
authors.lastname: Son
authors.affiliation: Department of Cell and Developmental Biology, Epigenetics Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA;
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonasio
authors.affiliation: Center for Health Informatics and Bioinformatics, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York, 10016, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Shen
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Pharmacology, New York University Langone School of Medicine, New York 10016, USA;
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000818:Animals; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000502:physiology; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006657:Histones / Q000378:metabolism; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D061987:Sf9 Cells
chemical_list: D006657:Histones; C093650:Jarid2 protein, mouse; D012313:RNA; D063151:Polycomb Repressive Complex 2
keywords: EZH2; JARID2; PRC2; chromatin; ncRNA