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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2023,6,6]]},"abstract":"<jats:p>The chromatin-modifying enzyme, Polycomb Repressive Complex 2 (PRC2), deposits the H3K27me3 epigenetic mark to negatively regulate expression at numerous target genes, and this activity has been implicated in embryonic development, cell differentiation, and various cancers. A biological role for RNA binding in regulating PRC2 histone methyltransferase activity is generally accepted, but the nature and mechanism of this relationship remains an area of active investigation. Notably, many in\u00a0vitro studies demonstrate that RNA inhibits PRC2 activity on nucleosomes through mutually antagonistic binding, while some in\u00a0vivo studies indicate that PRC2\u2019s RNA-binding activity is critical for facilitating its biological function(s). Here we use biochemical, biophysical, and computational approaches to interrogate PRC2\u2019s RNA and DNA-binding kinetics. Our findings demonstrate that PRC2-polynucleotide dissociation rates are dependent on the concentration of free ligand, indicating the potential for direct transfer between nucleic acid ligands without a free-enzyme intermediate. Direct transfer explains the variation in previously reported dissociation kinetics, allows reconciliation of prior in\u00a0vitro and in\u00a0vivo studies, and expands the potential mechanisms of RNA-mediated PRC2 regulation. Moreover, simulations indicate that such a direct transfer mechanism could be obligatory for RNA to recruit proteins to chromatin.<\/jats:p>","DOI":"10.1073\/pnas.2220528120","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T13:31:38Z","timestamp":1685453498000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":20,"title":["PRC2 direct transfer from G-quadruplex RNA to dsDNA has implications for RNA-binding chromatin modifiers"],"prefix":"10.1073","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8136-1574","authenticated-orcid":false,"given":"Wayne\u00a0O.","family":"Hemphill","sequence":"first","affiliation":[{"name":"Department of Biochemistry, BioFrontiers Institute, University of Colorado Boulder, Boulder, CO 80309"},{"name":"HHMI, University of Colorado Boulder, Boulder, CO 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