Cell Reports
Volume 12, Issue 9, 1 September 2015, Pages 1456-1470
Journal home page for Cell Reports

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

https://doi.org/10.1016/j.celrep.2015.07.053Get rights and content
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Highlights

  • PRC2 is required to maintain expression of the maternal Gtl2-Rian-Mirg locus

  • PRC2 transcriptionally regulates the Gtl2-Rian-Mirg locus through DNAme at IG-DMR

  • IG-DMR serves as an enhancer of the maternal Gtl2-Rian-Mirg locus

  • PRC2 prevents de novo DNAme at IG-DMR for maternal Gtl2-Rian-Mirg locus expression

Summary

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.

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This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Co-first author

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Present address: Department of Medicine and Cancer Center, Weill Cornell Medical College, Belfer Research Building, 413 East 69th Street, New York, NY 10021, USA

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Present address: Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

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Present address: Children’s Medical Center Research Institute and Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, TX 75235, USA

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Present address: Tsinghua-Peking Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China

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Present address: Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, Center for Systems and Synthetic Biology, The University of Texas, Austin, Austin, TX 78712, USA