title: Vitamin C promotes widespread yet specific DNA demethylation of the epigenome in human embryonic stem cells.
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.
authors.affiliation: Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Tung-Liang
authors.initials: TL
authors.lastname: Chung
authors.forename: Romulo M
authors.initials: RM
authors.lastname: Brena
authors.forename: Gabriel
authors.initials: G
authors.lastname: Kolle
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Berman
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
authors.forename: Ernst Jurgen
authors.initials: EJ
authors.lastname: Wolvetang
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D019175:DNA Methylation / Q000187:drug effects* / Q000235:genetics; D053595:Embryonic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
chemical_list: D056484:Jumonji Domain-Containing Histone Demethylases; D001205:Ascorbic Acid