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  X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs

Pasque, V., Karnik, R., Chronis, C., Petrella, P., Langerman, J., Bonora, G., et al. (2018). X Chromosome Dosage Influences DNA Methylation Dynamics during Reprogramming to Mouse iPSCs. Stem Cell Reports, 10(5), 1537-1550. doi:10.1016/j.stemcr.2018.03.019.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-4BA0-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-4BA1-3
Genre: Journal Article

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© 2018 The Author(s)

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 Creators:
Pasque, Vincent , Author
Karnik, Rahul , Author
Chronis, Constantinos, Author
Petrella, Paula , Author
Langerman, Justin, Author
Bonora, Giancarlo , Author
Song, Juan , Author
Vanheer, Lotte , Author
Dimashkie, Anupama Sadhu , Author
Meissner, Alexander1, 2, Author              
Plath, Kathrin , Author
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Harvard Stem Cell Institute, Broad Institute of MIT and Harvard, Cambridge, MA 02138, USA, ou_persistent22              

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Free keywords: DNA methylation; ESC; X chromosome inactivation; embryonic stem cells; epigenetics; iPSC; induced pluripotency; pluripotency; reprogramming
 Abstract: A dramatic difference in global DNA methylation between male and female cells characterizes mouse embryonic stem cells (ESCs), unlike somatic cells. We analyzed DNA methylation changes during reprogramming of male and female somatic cells and in resulting induced pluripotent stem cells (iPSCs). At an intermediate reprogramming stage, somatic and pluripotency enhancers are targeted for partial methylation and demethylation. Demethylation within pluripotency enhancers often occurs at ESC binding sites of pluripotency transcription factors. Late in reprogramming, global hypomethylation is induced in a female-specific manner. Genome-wide hypomethylation in female cells affects many genomic landmarks, including enhancers and imprint control regions, and accompanies the reactivation of the inactive X chromosome. The loss of one of the two X chromosomes in propagating female iPSCs is associated with genome-wide methylation gain. Collectively, our findings highlight the dynamic regulation of DNA methylation at enhancers during reprogramming and reveal that X chromosome dosage dictates global DNA methylation levels in iPSCs.

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Language(s): eng - English
 Dates: 2018-03-222018-04-192018-05-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.stemcr.2018.03.019
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Title: Stem Cell Reports
Source Genre: Journal
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Publ. Info: Cell Press
Pages: 14 Volume / Issue: 10 (5) Sequence Number: - Start / End Page: 1537 - 1550 Identifier: ISSN: 2213-6711