Tet enzymes regulate DNA methylation by converting 5-methylcytosine to 5-hydroxymethylcytosine and other oxidized variants. Vitamin C is a co-factor of enzymes of the same family as Tet enzymes. Here it is shown to be a direct regulator of Tet activity in mouse embryonic stem cells, which are typically cultured in the absence of vitamin C. The addition of vitamin C to the culture medium leads to increased 5-hydroxymethylcytosine content and the demethylation of numerous gene promoters. The remodelled DNA methylation and gene expression patterns are reminiscent of the DNA demethylation that occurs in the inner cell mass of the early embryo.
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