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Make sure you take your vitamin C!

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The principal observation is that vitamin C promotes DNA demethylation of the hESC genome however this is by no means universal applicable to all genomic regions. Ascorbate-mediated DNA methylation occurs genome-wide, but specifically affects a subset of 1,847 genes and causes altered expression of a subset of these genes. Interestingly, ascorbate mediated DNA demethylation occurs most frequently at CpGs near the edges of a CpG island. These are of particular relevance to pluripotent stem cells since they frequently contain differentially methylated regions that undergo hypomethylation during reprogramming of somatic cells(2) and those early developmental genes marked by bivalent chromatin domains (3). The data of Chung et al suggest that vitamin C specifically alters the methylation of shore CGIs that are associated with tissue-specific DNA methylation and reprogramming. Ascorbate induced demethylation of DNA has been observed by other workers (4) and its inhibition of histone demethylases has been described (5) but this is the first report of a DNA demethylating effect on an exact set of genes important for the establishment and maintenance of pluripotency. It is difficult to image how simply inhibiting the activity of an enzyme involved in demethylating lysines on the N-terminal tails of histones could achieve such specificity of action so it is clear that this is only the beginning of a much larger story.

 

  1. Cell Stem Cell. 2010 Jan 8;6(1):71-9
  2. Nat Genet 2009;41:178–186.
  3. Cell. 2006 Apr 21;125(2):315-26
  4. Hum Mol Genet 2007;16:1253–1268.
  5. Nat Rev Genet 2007;8:829–833.