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Protein Arginine Methyltransferase 6 Regulates Embryonic Stem Cell Identity

Lee, Yun Hwa and Ma, Hui and Tan, Tuan Zea and Ng, Swee Siang and Soong, Richie and Mori, Seiichi and Fu, Xin-Yuan and Zernicka-Goetz, Magdalena and Wu, Qiang (2012) Protein Arginine Methyltransferase 6 Regulates Embryonic Stem Cell Identity. Stem Cells and Development, 21 (14). pp. 2613-2622. ISSN 1547-3287. PMCID PMC5729635. doi:10.1089/scd.2011.0330. https://resolver.caltech.edu/CaltechAUTHORS:20190417-152709819

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Abstract

Histone arginine methylation has emerged as an important histone modification involved in gene regulation. Protein arginine methyltransferase (PRMT) 4 and 5 have been shown to play essential roles in early embryonic development and in embryonic stem (ES) cells. Recently, it has been reported that PRMT6-mediated di-methylation of histone H3 at arginine 2 (H3R2me2) can antagonize tri-methylation of histone H3 at lysine 4 (H3K4me3), which marks active genes. However, whether PRMT6 and PRMT6-mediated H3R2me2 play crucial roles in early embryonic development and ES cell identity remain unclear. Here, we have investigated their roles using gain and loss of function studies with mouse ES cells as a model system. We report that Prmt6 and histone H3R2 methylation levels increased when ES cells are induced to differentiate. Consistently, we find that differentiation of ES cells upon upregulation of Prmt6 is associated with decreased expression of pluripotency genes and increased expression of differentiation markers. We also observe that elevation of Prmt6 increases the methylation level of histone H3R2 and decreases H3K4me, Chd1, and Wdr5 levels at the promoter regions of Oct4 and Nanog. Surprisingly, knockdown of Prmt6 also leads to downregulation of pluripotency genes and induction of expression of differentiation markers suggesting that Prmt6 is important for ES cell pluripotency and self-renewal. Our results indicate that a critical level of Prmt6 and histone H3R2me must be maintained in mouse ES cells to sustain their pluripotency.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1089/scd.2011.0330DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5729635/PubMed CentralArticle
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2012 Mary Ann Liebert, Inc. Received for publication June 27, 2011. Accepted after revision March 27, 2012. Prepublished on Liebert Instant Online March 28, 2012. We thank Eunice Lin and Soheila Sharghi Namini for critical reading of the article. We thank Ernesto Guccione for valuable discussion and for providing anti-histone H3R2me2 serum. M.Z.G. is supported by the Wellcome Trust. Research in Q. Wu's lab is supported by the National University of Singapore (NUS) and the Singapore Ministry of Education. No competing financial interests exist.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
National University of SingaporeUNSPECIFIED
Ministry of Education (Singapore)UNSPECIFIED
Issue or Number:14
PubMed Central ID:PMC5729635
DOI:10.1089/scd.2011.0330
Record Number:CaltechAUTHORS:20190417-152709819
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190417-152709819
Official Citation:Yun Hwa Lee, Hui Ma, Tuan Zea Tan, Swee Siang Ng, Richie Soong, Seiichi Mori, Xin-Yuan Fu, Magdalena Zernicka-Goetz, and Qiang Wu.Stem Cells and Development.Sep 2012.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94759
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:17 Apr 2019 23:16
Last Modified:16 Nov 2021 17:07

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