Vitamin C Promotes Widespread Yet Specific DNA Demethylation of the Epigenome in Human Embryonic Stem Cells (original) (raw)

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Australian Institute for Bioengineering and Nanotechnology, The University of Queensland

, Brisbane, Queensland,

Australia

Australian Stem Cell Centre

, Melbourne, Victoria,

Australia

Monash Institute of Medical Research, Monash University

, Melbourne, Victoria,

Australia

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USC Epigenome Center, Keck School of Medicine, University of Southern California

, Los Angeles, California,

USA

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Institute for Molecular Bioscience, The University of Queensland

, Brisbane, Queensland,

Australia

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Institute for Molecular Bioscience, The University of Queensland

, Brisbane, Queensland,

Australia

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USC Epigenome Center, Keck School of Medicine, University of Southern California

, Los Angeles, California,

USA

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USC Epigenome Center, Keck School of Medicine, University of Southern California

, Los Angeles, California,

USA

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Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of Southern California

, Los Angeles, California,

USA

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Australian Institute for Bioengineering and Nanotechnology, The University of Queensland

, Brisbane, Queensland,

Australia

Correspondence: Ernst Jurgen Wolvetang, PhD, Australian Institute for Bioengineering and Nanotechnology (AIBN), Corner College and Cooper Rds (Bldg 75), The University of Queensland, Brisbane Qld 4,072 Australia. Telephone: 61-7-33463894; Fax: 61-7-33463973; e-mail e.wolvetang@uq.edu.au

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Published:

26 October 2010

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Tung-Liang Chung, Romulo M. Brena, Gabriel Kolle, Sean M. Grimmond, Benjamin P. Berman, Peter W. Laird, Martin F. Pera, Ernst Jurgen Wolvetang, Vitamin C Promotes Widespread Yet Specific DNA Demethylation of the Epigenome in Human Embryonic Stem Cells , Stem Cells, Volume 28, Issue 10, October 2010, Pages 1848–1855, https://doi.org/10.1002/stem.493
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Abstract

Vitamin C (ascorbate) is a widely used medium supplement in embryonic stem cell culture. Here, we show that ascorbate causes widespread, consistent, and remarkably specific DNA demethylation of 1,847 genes in human embryonic stem cells (hESCs), including important stem cell genes, with a clear bias toward demethylation at CpG island boundaries. We show that a subset of these DNA demethylated genes displays concomitant gene expression changes and that the position of the demethylated CpGs relative to the transcription start site is correlated to such changes. We further show that the ascorbate-demethylated gene set not only overlaps with gene sets that have bivalent marks, but also with the gene sets that are demethylated during differentiation of hESCs and during reprogramming of fibroblasts to induced pluritotent stem cells (iPSCs). Our data thus identify a novel link between ascorbate-mediated signaling and specific epigenetic changes in hESCs that might impact on pluripotency and reprogramming pathways.

Copyright © 2010 AlphaMed Press

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open\_access/funder\_policies/chorus/standard\_publication\_model)

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