Breathing-in epigenetic change with vitamin C
Open accessAbstract
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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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 measuredJumonji-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].”
From Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination (2021) · cites this paper as [107]
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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“However, ascorbate is often absent from the media for culturing various cells including melanoma cells (33).”
BackgroundPharmacokinetic modeling of ascorbate diffusion through normal and tumor tissue
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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
- PMC
- PMC3615655
- 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
- bronze
- doi.org
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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