Cited by 140Epigenetics and DNA MethylationPluripotent Stem Cells ResearchVitamin C and Antioxidants Research

Breathing-in epigenetic change with vitamin C

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Monfort, Asun, Wutz, Anton·2013·The EMBO Reports

Abstract

Vitamin C is an antioxidant that maintains the activity of iron and α-ketoglutarate-dependent dioxygenases. Despite these enzymes being implicated in a wide range of biological pathways, vitamin C is rarely included in common cell culture media. Recent studies show that reprogramming of pluripotent stem cells is enhanced when vitamin C is present, thereby illustrating previous limitations in reprogramming cultures. Here, we summarize understanding of dioxygenase function in reprogramming and epigenetic regulation. The available data suggest a link between dioxygenase function and stem cell differentiation, which is exposed to environmental influence and is relevant for human disease.

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Crossref · 10.1038/embor.2013.29

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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 [107]

    The section “Dioxygenases contribute to epigenetic regulation” says vitamin C has a crucial role in Fe(II)-2OG-dependent dioxygenase activity and links these enzymes to histone and DNA methylation. The Introduction also links vitamin C to the hypoxia-response pathway. But it says vitamin C is not absolutely essential and can, in some cases, be replaced by other antioxidants, so “the specific cofactor” overstates the evidence. (LLM, conf=0.88)

    Experimental — accuracy not yet measured
  • Jumonji-C (JmjC) domain-containing proteins are responsible for hydroxylation of specific histone lysines leading to histone demethylation.

    “One of the most known enzyme groups are Jumonji-C (JmjC) domain-containing proteins responsible for hydroxylation of specific histone lysines leading to histone demethylation (JmjC demethylases, e.g., JHDMs and KDMs families) [107,112,113,114].”
  • Vitamin C may regulate other αKGDD epigenetic enzymes, including JHDM and ALKB.

    “other αKGDDs such as JmjC domain-containing histone demethylase family (JHDM) and αKGDD AlkB (ALKB) are also known to be epigenetic regulators that can be potentially regulated by vitamin C73,74.”

    From Targeting cancer vulnerabilities with high-dose vitamin C (2019) · cites this paper as [73]

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Authors
Monfort, A., & Wutz, A.
Affiliations
Wellcome/MRC Cambridge Stem Cell Institute (GB)
Corresponding author
Wutz, Anton
Venue
The EMBO Reports
Published
2013-03-15
Volume
14
Issue
4
Pages
337-346
ISSN
  • 1469-221X (ISSN-L)
  • 1469-3178
OpenAlex
W2167110353
Cited by
140
References
111
Citations by year
2026: 3 · 2025: 7 · 2024: 8 · 2023: 9 · 2022: 8 · 2021: 8 · 2020: 11 · 2019: 16 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 12 · 2014: 15 · 2013: 5
FWCI
1.35
Type
journal article
Language
en
Open access
Locations
  • EMBO Reports (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust (087530, 087530/Z/08/A, 079249)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords
vitamin C, epigenetic regulation, dioxygenase, iron-dependent dioxygenase, alpha-ketoglutarate-dependent dioxygenase, stem cell differentiation, cell culture media
MeSH terms
Animals, Antioxidants, Ascorbic Acid, Cell Differentiation, DNA-Binding Proteins, Humans, Oxidation-Reduction, Proto-Oncogene Proteins, DNA Methylation, Epigenesis, Genetic, Dioxygenases, Histone Demethylases, Induced Pluripotent Stem Cells

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