Howard Hughes Medical Institute and NYU School of Medicine, Department of Molecular Pharmacology and Biochemistry, New York, NY 10016, USA.
National Research Institute for Child Health and Development, Department of Reproductive Biology, Tokyo 157-8535, Japan.
Mol Cell. 2014 Jan 23;53(2):290-300. doi: 10.1016/j.molcel.2013.11.012. Epub 2013 Dec 26.
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.
JARID2 是多梳抑制复合物 2（PRC2）的辅助成分，对于胚胎干细胞（ESCs）的分化是必需的。已经提出了 JARID2 在募集 PRC2 到分化过程中沉默的靶基因中的作用，但分子细节仍不清楚。我们鉴定了 JARID2 与长链非编码 RNA（lncRNA）相互作用的 30 个氨基酸区域，并发现 lncRNA 的存在刺激了 JARID2-EZH2 相互作用在体外和 JARID2 介导的 PRC2 到染色质的募集在体内。JARID2 的天然和交联 RNA 免疫沉淀显示，印迹 Dlk1-Dio3 基因座的 Meg3 和其他 lncRNA，是发育的重要调节剂，通过 JARID2 与 PRC2 相互作用。人诱导多能细胞中 MEG3 的缺失改变了 JARID2、PRC2 和 H3K27me3 的染色质分布。我们的发现表明 lncRNA 促进了染色质上 JARID2-PRC2 的相互作用，并提出了 lncRNA 有助于 PRC2 募集的机制。
