title: Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin.
abstract: JARID2 is an accessory component of Polycomb repressive complex-2 (PRC2) required for the differentiation of embryonic stem cells (ESCs). A role for JARID2 in the recruitment of PRC2 to target genes silenced during differentiation has been put forward, but the molecular details remain unclear. We identified a 30-amino-acid region of JARID2 that mediates interactions with long noncoding RNAs (lncRNAs) and found that the presence of lncRNAs stimulated JARID2-EZH2 interactions in vitro and JARID2-mediated recruitment of PRC2 to chromatin in vivo. Native and crosslinked RNA immunoprecipitations of JARID2 revealed that Meg3 and other lncRNAs from the imprinted Dlk1-Dio3 locus, an important regulator of development, interacted with PRC2 via JARID2. Lack of MEG3 expression in human induced pluripotent cells altered the chromatin distribution of JARID2, PRC2, and H3K27me3. Our findings show that lncRNAs facilitate JARID2-PRC2 interactions on chromatin and suggest a mechanism by which lncRNAs contribute to PRC2 recruitment.
authors.affiliation: Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA.
authors.forename: Syuzo
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bonasio
authors.affiliation: Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Saldaña-Meyer
authors.affiliation: National Research Institute for Child Health and Development, Department of Reproductive Biology, Tokyo 157-8535, Japan.
authors.forename: Takahaki
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA.
authors.forename: Jinsook
authors.initials: J
authors.lastname: Son
authors.affiliation: University of Miyazaki, Faculty of Agriculture, Laboratory of Veterinary Biochemistry and Molecular Biology, Miyazaki 889-2192, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nishino
authors.affiliation: National Research Institute for Child Health and Development, Department of Reproductive Biology, Tokyo 157-8535, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA. Electronic address: Danny.Reinberg@nyumc.org.
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D000071221:Enhancer of Zeste Homolog 2 Protein; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D051379:Mice; D063151:Polycomb Repressive Complex 2 / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology*; D062085:RNA, Long Noncoding / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*
chemical_list: D002843:Chromatin; C547777:JARID2 protein, human; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2