Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells

Chung, TL, Brena, RM, Kolle, G, Grimmond, SM, Berman, BP, Laird, PW, Pera, MF and Wolvetang, EJ (2010) Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells. Stem Cells, 28 10: 1848-1855. doi:10.1002/stem.493


Author Chung, TL
Brena, RM
Kolle, G
Grimmond, SM
Berman, BP
Laird, PW
Pera, MF
Wolvetang, EJ
Title Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells
Journal name Stem Cells   Check publisher's open access policy
ISSN 1066-5099
1549-4918
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1002/stem.493
Volume 28
Issue 10
Start page 1848
End page 1855
Total pages 8
Place of publication Durham, NC, U.S.A.
Publisher AlphaMed Press
Collection year 2011
Language eng
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. © AlphaMed Press.
Keyword Human embryonic stem cells
Epigenetic changes
DNA hypomethylation
CpG shores
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

 
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Created: Sun, 05 Dec 2010, 00:00:58 EST