4.3 Review

Ascorbic Acid in Epigenetic Reprogramming

Journal

CURRENT STEM CELL RESEARCH & THERAPY
Volume 17, Issue 1, Pages 13-25

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1574888X16666210714152730

Keywords

Vitamin C; reprogramming; DNA demethylation; histone demethylation; RNA demethylation; iron and 2-oxoglutarate dependent dioxygenases; somatic cell regeneration

Funding

  1. National Natural Science Foundation of China [81702802]
  2. Beijing Municipal Commission of Education [KM-201810005032, KM20191000 5005]

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Emerging evidence suggests that vitamin C enhances the reprogramming process by acting as a cofactor in DNA and histone demethylation. It also potentially plays a role in regulating RNA methylation and cellular reprogramming. This review highlights the significance of vitamin C in epigenetic regulation and its affiliation with demethylases in facilitating epigenetic reprogramming.
Emerging evidence suggests that ascorbic acid (vitamin C) enhances the reprogramming process by multiple mechanisms primarily due to its cofactor role in Fe(II) and 2-oxoglutarate-dependent dioxygenases, including the DNA demethylases Ten Eleven Translocase (TET) and histone demethylases. Epigenetic variations have been shown to play a critical role in somatic cell reprogramming. DNA methylation and histone methylation are extensively recognized as barriers to somatic cell reprogramming. N-6-methyladenosine (m(6)A), known as RNA methylation, is an epigenetic modification of mRNAs and has also been shown to play a role in regulating cellular reprogramming. Multiple cofactors are reported to promote the activity of these demethylases, including vitamin C. Therefore, this review focuses and examines the evidence and mechanism of vitamin C in DNA and histone demethylation and highlights its potential involvement in the regulation of m(6)A demethylation. It also shows the significant contribution of vitamin C in epigenetic regulation, and the affiliation of demethylases with vitamin C-facilitated epigenetic reprogramming.

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