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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 545-564 |
| Number of pages | 20 |
| Journal | Annual Review of Nutrition |
| Volume | 35 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 17 2015 |
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Keywords
- DNA demethylation
- Histone demethylation
- Iron- and 2-oxoglutarate-dependent dioxygenase
- JmjC-domain-containing histone demethylase
- Ten-eleven translocation dioxygenase
- Vitamin C
ASJC Scopus subject areas
- Medicine (miscellaneous)
- Nutrition and Dietetics
Cite this
Regulation of the Epigenome by Vitamin C. / Young, Juan; Zuchner, Stephan L; Wang, Gaofeng.
In: Annual Review of Nutrition, Vol. 35, No. 1, 17.07.2015, p. 545-564.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Regulation of the Epigenome by Vitamin C
AU - Young, Juan
AU - Zuchner, Stephan L
AU - Wang, Gaofeng
PY - 2015/7/17
Y1 - 2015/7/17
N2 - 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.
AB - 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.
KW - DNA demethylation
KW - Histone demethylation
KW - Iron- and 2-oxoglutarate-dependent dioxygenase
KW - JmjC-domain-containing histone demethylase
KW - Ten-eleven translocation dioxygenase
KW - Vitamin C
UR - http://www.scopus.com/inward/record.url?scp=84937538653&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84937538653&partnerID=8YFLogxK
U2 - 10.1146/annurev-nutr-071714-034228
DO - 10.1146/annurev-nutr-071714-034228
M3 - Article
C2 - 25974700
AN - SCOPUS:84937538653
VL - 35
SP - 545
EP - 564
JO - Annual Review of Nutrition
JF - Annual Review of Nutrition
SN - 0199-9885
IS - 1
ER -