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G-tract RNA removes Polycomb repressive complex 2 from genes.
Nat. Struct. Mol. Biol. 26, 899-909 (2019)
Polycomb repressive complex 2 (PRC2) maintains repression of cell-type-specific genes but also associates with genes ectopically in cancer. While it is currently unknown how PRC2 is removed from genes, such knowledge would be useful for the targeted reversal of deleterious PRC2 recruitment events. Here, we show that G-tract RNA specifically removes PRC2 from genes in human and mouse cells. PRC2 preferentially binds G tracts within nascent precursor mRNA (pre-mRNA), especially within predicted G-quadruplex structures. G-quadruplex RNA evicts the PRC2 catalytic core from the substrate nucleosome. In cells, PRC2 transfers from chromatin to pre-mRNA upon gene activation, and chromatin-associated G-tract RNA removes PRC2, leading to H3K27me3 depletion from genes. Targeting G-tract RNA to the tumor suppressor gene CDKN2A in malignant rhabdoid tumor cells reactivates the gene and induces senescence. These data support a model in which pre-mRNA evicts PRC2 during gene activation and provides the means to selectively remove PRC2 from specific genes.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Demethylase Jmjd3 Contributes; G-quadruplex Structures; Enhancer Activity; Prc2 Recruitment; Ezh2; Dna; Chromatin; Transcription; Inhibition; Reveals
ISSN (print) / ISBN
1545-9993
e-ISSN
1545-9985
Zeitschrift
Nature Structural & Molecular Biology
Quellenangaben
Band: 26,
Heft: 10,
Seiten: 899-909
Verlag
Nature Publishing Group
Verlagsort
New York, NY
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Functional Epigenetics (IFE)