| Literature DB >> 26299972 |
Partha Pratim Das1, David A Hendrix2, Effie Apostolou3, Alice H Buchner4, Matthew C Canver5, Semir Beyaz5, Damir Ljuboja5, Rachael Kuintzle6, Woojin Kim5, Rahul Karnik7, Zhen Shao5, Huafeng Xie5, Jian Xu5, Alejandro De Los Angeles5, Yingying Zhang7, Junho Choe8, Don Leong Jia Jun9, Xiaohua Shen5, Richard I Gregory8, George Q Daley1, Alexander Meissner7, Manolis Kellis10, Konrad Hochedlinger11, Jonghwan Kim5, Stuart H Orkin12.
Abstract
Polycomb Repressive Complex 2 (PRC2) function and DNA methylation (DNAme) are typically correlated with gene repression. Here, we show that PRC2 is required to maintain expression of maternal microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) from the Gtl2-Rian-Mirg locus, which is essential for full pluripotency of iPSCs. In the absence of PRC2, the entire locus becomes transcriptionally repressed due to gain of DNAme at the intergenic differentially methylated regions (IG-DMRs). Furthermore, we demonstrate that the IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus. Further analysis reveals that PRC2 interacts physically with Dnmt3 methyltransferases and reduces recruitment to and subsequent DNAme at the IG-DMR, thereby allowing for proper expression of the maternal Gtl2-Rian-Mirg locus. Our observations are consistent with a mechanism through which PRC2 counteracts the action of Dnmt3 methyltransferases at an imprinted locus required for full pluripotency.Entities:
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Year: 2015 PMID： 26299972 PMCID： PMC5384103 DOI： 10.1016/j.celrep.2015.07.053
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423