title: Regulation of the Epigenome by Vitamin C.
abstract: Emerging evidence suggests that ascorbate, the dominant form of vitamin C under physiological pH conditions, influences activity of the genome via regulating epigenomic processes. Ascorbate serves as a cofactor for Ten-eleven translocation (TET) dioxygenases that catalyze the oxidation of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), and further to 5-formylcytosine (5fC) and to 5-carboxylcytosine (5caC), which are ultimately replaced by unmodified cytosine. The Jumonji C (JmjC)-domain-containing histone demethylases also require ascorbate as a cofactor for histone demethylation. Thus, by primarily participating in the demethylation of both DNA and histones, ascorbate appears to be a mediator of the interface between the genome and environment. Furthermore, redox status has a profound impact on the bioavailability of ascorbate in the nucleus. In order to bridge the gap between redox biology and genomics, we suggest an interdisciplinary research field that can be termed redox genomics to study dynamic redox processes in health and diseases. This review examines the evidence and potential molecular mechanism of ascorbate in the demethylation of the genome, and it highlights potential epigenetic roles of ascorbate in various diseases.
authors.affiliation: John P. Hussman Institute for Human Genomics.
authors.forename: Juan I
authors.initials: JI
authors.lastname: Young
authors.forename: Stephan
authors.initials: S
authors.lastname: Züchner
authors.forename: Gaofeng
authors.initials: G
authors.lastname: Wang
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology*; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D049308:Dioxygenases / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000187:drug effects*; D056466:Histone Demethylases / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D010084:Oxidation-Reduction
chemical_list: D003596:Cytosine; D049308:Dioxygenases; D056466:Histone Demethylases; D001205:Ascorbic Acid
keywords: DNA demethylation; JmjC-domain-containing histone demethylase; Ten-eleven translocation dioxygenase; histone demethylation; iron- and 2-oxoglutarate-dependent dioxygenase; vitamin C