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

Das, P. P., Hendrix, D. A., Apostolou, E., Buchner, A. H., Canver, M. C., Beyaz, S., Ljuboja, D., Kuintzle, R., Kim, W., Karnik, R., Shao, Z., Xie, H., Xu, J., De Los Angeles, A., Zhang, Y., Choe, J., Jun, D. L., Shen, X., Gregory, R. I., Daley, G. Q., Meissner, A., Kellis, M., Hochedlinger, K., Kim, J., Orkin, S. H. (September 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 Rep, 12 (9). pp. 1456-70. ISSN 2211-1247 (Electronic)

URL: https://www.ncbi.nlm.nih.gov/pubmed/26299972
DOI: 10.1016/j.celrep.2015.07.053

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.

Item Type: Paper
Uncontrolled Keywords: Animals Cell Line DNA (Cytosine-5-)-Methyltransferases/metabolism *DNA Methylation Embryonic Stem Cells/*metabolism *Genomic Imprinting Mice MicroRNAs/genetics Nuclear Proteins/genetics Polycomb Repressive Complex 2/genetics/*metabolism Protein Binding RNA, Long Noncoding/*genetics
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > polycomb group genes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > stem cells
CSHL Authors:
Communities: CSHL labs > Beyaz lab
Depositing User: Matt Covey
Date: 1 September 2015
Date Deposited: 01 Feb 2018 21:50
Last Modified: 01 Feb 2018 21:50
PMCID: PMC5384103
Related URLs:
URI: http://repository.cshl.edu/id/eprint/36049

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