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CARM1 Is Required in Embryonic Stem Cells to Maintain Pluripotency and Resist Differentiation

Wu, Qiang and Bruce, Alexander W. and Jedrusik, Agnieszka and Ellis, Peter D. and Andrews, Robert M. and Langford, Cordelia F. and Glover, David M. and Zernicka-Goetz, Magdalena (2009) CARM1 Is Required in Embryonic Stem Cells to Maintain Pluripotency and Resist Differentiation. Stem Cells, 27 (11). pp. 2637-2645. ISSN 1066-5099. PMCID PMC4135545. https://resolver.caltech.edu/CaltechAUTHORS:20190417-163115057

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[img] Image (TIFF) (Supplementary Fig. 1: CARM1 RNAi induced ES cell differentiation phenotype is specific and can be rescued by over‐expression of an RNAi resistant CARM1 cDNA) - Supplemental Material
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[img] Image (TIFF) (Supplementary Fig. 2: CARM1 and histone arginine methylation marks are removed from the Oct4 and Sox2 promoters after CARM1 depletion) - Supplemental Material
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[img] Image (TIFF) (Supplementary Fig. 3: Levels of CARM1 and Nanog in CARM1 over‐expressing ES cells) - Supplemental Material
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[img] Image (TIFF) (Supplementary Fig. 4: Progeny of ES cells expressing elevated CARM1 levels contribute to ICM of mouse blastocysts) - Supplemental Material
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[img] Image (TIFF) (Supplementary Fig. 5: Self‐renewal capacity of CARM1 over‐expressing cells and wide‐type ES cells) - Supplemental Material
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[img] Image (TIFF) (Supplementary Fig. 6: CARM1 over‐expression leads ES cell to resist differentiation following LIF‐removal ) - Supplemental Material
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[img] MS Excel (Supplementary Information 1: Differentially expressed genes after CARM1 RNAi) - Supplemental Material
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[img] MS Excel (Supplementary Information 2: Gene names in each CARM1 RNAi gene cluster) - Supplemental Material
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[img] MS Excel (Supplementary Information 3: Gene clusters in GO terms.) - Supplemental Material
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Abstract

Histone H3 methylation at R17 and R26 recently emerged as a novel epigenetic mechanism regulating pluripotency in mouse embryos. Blastomeres of four‐cell embryos with high H3 methylation at these sites show unrestricted potential, whereas those with lower levels cannot support development when aggregated in chimeras of like cells. Increasing histone H3 methylation, through expression of coactivator‐associated‐protein‐arginine‐methyltransferase 1 (CARM1) in embryos, elevates expression of key pluripotency genes and directs cells to the pluripotent inner cell mass. We demonstrate CARM1 is also required for the self‐renewal and pluripotency of embryonic stem (ES) cells. In ES cells, CARM1 depletion downregulates pluripotency genes leading to their differentiation. CARM1 associates with Oct4/Pou5f1 and Sox2 promoters that display detectable levels of R17/26 histone H3 methylation. In CARM1 overexpressing ES cells, histone H3 arginine methylation is also at the Nanog promoter to which CARM1 now associates. Such cells express Nanog at elevated levels and delay their response to differentiation signals. Thus, like in four‐cell embryo blastomeres, histone H3 arginine methylation by CARM1 in ES cells allows epigenetic modulation of pluripotency.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1002/stem.131DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135545/PubMed CentralArticle
ORCID:
AuthorORCID
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2009 AlphaMed Press. Received October 29, 2008; accepted for publication April 30, 2009; first published online in STEM CELLS EXPRESS May 21, 2009; available online without subscription through the open access option. © AlphaMed Press. MZG is grateful to the Wellcome Trust for a Senior Research Fellowship and associated program grant that supported this work. We are grateful to Ian Chambers for cell lines and advice and Paul Robson for valuable comments. The authors indicate no potential conflict of interest.
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Subject Keywords:CARM1 • ES cells • pluripotency • differentiation • chromatin • arginine histone methylation
Issue or Number:11
PubMed Central ID:PMC4135545
Record Number:CaltechAUTHORS:20190417-163115057
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190417-163115057
Official Citation:Wu, Q. , Bruce, A. W., Jedrusik, A. , Ellis, P. D., Andrews, R. M., Langford, C. F., Glover, D. M. and Zernicka‐Goetz, M. (2009), CARM1 Is Required in Embryonic Stem Cells to Maintain Pluripotency and Resist Differentiation. STEM CELLS, 27: 2637-2645. doi:10.1002/stem.131
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94774
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:18 Apr 2019 14:38
Last Modified:03 Oct 2019 21:07

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