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  DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells

Choi, J., Clement, K., Huebner, A. J., Webster, J., Etchegaray, J.-P., Gu, H., et al. (2017). DUSP9 Modulates DNA Hypomethylation in Female Mouse Pluripotent Stem Cells. Cell Stem Cell, 20(5), 706-719. doi:10.1016/j.stem.2017.03.002.

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 Creators:
Choi, Jiho , Author
Clement, Kendell , Author
Huebner, Aaron J. , Author
Webster, Jamie , Author
Etchegaray, Jean-Pierre , Author
Gu, Hongcang , Author
Boyle, Patrick , Author
Elling, Ulrich , Author
Mostoslavsky, Raul, Author
Sadreyev, Ruslan , Author
Park, Peter J. , Author
Gygi, Steven P. , Author
Meissner, Alexander1, 2, 3, 4, Author              
Hochedlinger, Konrad , Author
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA, ou_persistent22              
3Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA, ou_persistent22              
4Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA, ou_persistent22              

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Free keywords: DNA methylation; Dusp9; X chromosome; cell fusion; embryonic germ cells; embryonic stem cells; genomic imprinting; inner cell mass; pluripotency; primordial germ cells
 Abstract: Blastocyst-derived embryonic stem cells (ESCs) and gonad-derived embryonic germ cells (EGCs) represent two classic types of pluripotent cell lines, yet their molecular equivalence remains incompletely understood. Here, we compare genome-wide methylation patterns between isogenic ESC and EGC lines to define epigenetic similarities and differences. Surprisingly, we find that sex rather than cell type drives methylation patterns in ESCs and EGCs. Cell fusion experiments further reveal that the ratio of X chromosomes to autosomes dictates methylation levels, with female hybrids being hypomethylated and male hybrids being hypermethylated. We show that the X-linked MAPK phosphatase DUSP9 is upregulated in female compared to male ESCs, and its heterozygous loss in female ESCs leads to male-like methylation levels. However, male and female blastocysts are similarly hypomethylated, indicating that sex-specific methylation differences arise in culture. Collectively, our data demonstrate the epigenetic similarity of sex-matched ESCs and EGCs and identify DUSP9 as a regulator of female-specific hypomethylation.

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Language(s): eng - English
 Dates: 2017-03-302017-05-04
 Publication Status: Published in print
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.stem.2017.03.002
 Degree: -

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Title: Cell Stem Cell
Source Genre: Journal
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Publ. Info: Elsevier
Pages: - Volume / Issue: 20 (5) Sequence Number: - Start / End Page: 706 - 719 Identifier: -