PRC2 Is Required to Maintain Expression of the Maternal Gtl2-Rian-Mirg Locus by Preventing De Novo DNA Methylation in Mouse Embryonic Stem Cells.

Cell Rep
Authors
Keywords
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.

Year of Publication
2015
Journal
Cell Rep
Volume
12
Issue
9
Pages
1456-70
Date Published
2015 Sep 01
ISSN
2211-1247
URL
DOI
10.1016/j.celrep.2015.07.053
PubMed ID
26299972
Links
Grant list
F30 DK103359 / DK / NIDDK NIH HHS / United States
F30 DK103359-01A1 / DK / NIDDK NIH HHS / United States
U01HL100001 / HL / NHLBI NIH HHS / United States