Regulation of the epigenome by vitamin C
Open accessAbstract
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.
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Vitamin C is the specific cofactor of 2OGO involved in cellular stress-signalling and epigenetics.
“A relatively new discovery is the finding that vitamin C is the specific cofactor of 2OGO involved in cellular stress-signalling and epigenetics (reviewed in References [98,101,102,107,108,109]).”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [102]
The Introduction says vitamin C (ascorbate) is a cofactor for some iron- and 2-oxoglutarate-dependent dioxygenases involved in DNA and histone demethylation. The review therefore supports the epigenetics part, but the passages do not establish that vitamin C is the specific cofactor for the entire enzyme family or address its involvement in cellular stress-signalling. (LLM, conf=0.86)
Experimental — accuracy not yet measuredVitamin C is needed for myelin formation by Schwann cells.
“It is known that vitamin C is needed for myelin formation by Schwann cells”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [102]
There are reports claiming that vitamin C is not needed for 2OGO, but they were questioned since ferrous ions could at least briefly substitute the lack of vitamin C.
“There are also some reports claiming that vitamin C is not needed, but they were questioned since ferrous ions could, at least, briefly substitute the lack of vitamin C [102].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [102]
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References 102 · Cited by 319
- Authors
- Young, J. I., Züchner, S., & Wang, G.
- Affiliations
- Dr. John T. Macdonald Foundation (US)
- John P. Hussman Institute for Human Genomics,
- University of Miami (US)
- Corresponding author
- Wang, Gaofeng
- Venue
- Annual Review of Nutrition
- Publisher
- Annual Reviews
- Published
- 2015-07-17
- Volume
- 35
- Issue
- 1
- Pages
- 545-564
- ISSN
- 0199-9885 (ISSN-L)
- 1545-4312
- PMC
- PMC4506708
- OpenAlex
- W2141776504
- Cited by
- 319
- References
- 102
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 20 · 2023: 32 · 2022: 36 · 2021: 40 · 2020: 48 · 2019: 35 · 2018: 28 · 2017: 26 · 2016: 14 · 2015: 3
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annual Review of Nutrition (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS075764, R01NS089525)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Keywords
- vitamin C, epigenetics, DNA demethylation, histone demethylation, TET enzymes, 5-hydroxymethylcytosine, redox state, gene-environment interaction
- MeSH terms
- Ascorbic Acid, Cytosine, Homeostasis, Humans, Oxidation-Reduction, DNA Methylation, Epigenesis, Genetic, Dioxygenases, Histone Demethylases
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