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

http://ir.library.oregonstate.edu/concern/articles/vd66w187p

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  • 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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  • Das, P. P., Hendrix, D. A., Apostolou, E., Buchner, A. H., Canver, M. C., Beyaz, S., ... & Orkin, S. H. (2015). 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 Reports, 12(9), 1456-1470. doi:10.1016/j.celrep.2015.07.053
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  • description.provenance : Approved for entry into archive by Patricia Black(patricia.black@oregonstate.edu) on 2015-09-23T18:55:15Z (GMT) No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) HendrixDavidEECSPRC2RequiredMaintain.pdf: 3616899 bytes, checksum: 317d47897d49c54f8eaee871b8146329 (MD5) HendrixDavidEECSPRC2RequiredMaintainSupplementalInformationFiguresS1–S7andTablesS1–S7.pdf: 1269347 bytes, checksum: d757559582e13489f04b6df6d81ab6d8 (MD5)
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  • description.provenance : Made available in DSpace on 2015-09-23T18:55:15Z (GMT). No. of bitstreams: 3 license_rdf: 1370 bytes, checksum: cd1af5ab51bcc7a5280cf305303530e9 (MD5) HendrixDavidEECSPRC2RequiredMaintain.pdf: 3616899 bytes, checksum: 317d47897d49c54f8eaee871b8146329 (MD5) HendrixDavidEECSPRC2RequiredMaintainSupplementalInformationFiguresS1–S7andTablesS1–S7.pdf: 1269347 bytes, checksum: d757559582e13489f04b6df6d81ab6d8 (MD5) Previous issue date: 2015-09-01

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