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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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
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
Quellenangaben
Volume: 26,
Issue: 10,
Pages: 899-909
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute of Functional Epigenetics (IFE)