ArticleBiochemical and biophysical research communications2013
Ascorbate-induced generation of 5-hydroxymethylcytosine is unaffected by varying levels of iron and 2-oxoglutarate.
Article in Biochemical and biophysical research communications, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- Advancing TET Inhibitor Development: From Structural Insights to Biological Evaluation.ACS medicinal chemistry letters · 2025Article
- Article
- Vitamin C enhances co-localization of novel TET1 nuclear bodies with both Cajal and PML bodies in colorectal cancer cells.Epigenetics · 2024Article
- Vitamin C activates young LINE-1 elements in mouse embryonic stem cells via H3K9me3 demethylation.Epigenetics & chromatin · 2023Article
- Nutriepigenomics in Environmental-Associated Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Tet Enzymes-Mediated DNA 5hmC Modification in Cerebral Ischemic and Hemorrhagic Injury.Neurotoxicity research · 2022Review
- The Anti-Leukemia Effect of Ascorbic Acid: From the Pro-Oxidant Potential to the Epigenetic Role in Acute Myeloid Leukemia.Frontiers in cell and developmental biology · 2022Review
- TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes.Journal of neurochemistry · 2021Article
- Review
- The Multiple Roles of Ascorbate in the Abiotic Stress Response of Plants: Antioxidant, Cofactor, and Regulator.Frontiers in plant science · 2021Review
- The Role of 2-Oxoglutarate Dependent Dioxygenases in Gliomas and Glioblastomas: A Review of Epigenetic Reprogramming and Hypoxic Response.Frontiers in oncology · 2021Review
- Deoxyribonucleic Acid 5-Hydroxymethylation in Cell-Free Deoxyribonucleic Acid, a Novel Cancer Biomarker in the Era of Precision Medicine.Frontiers in cell and developmental biology · 2021Review
- Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine.International journal of molecular sciences · 2020Review
- Aberrant DNA methylation profile exacerbates inflammation and neurodegeneration in multiple sclerosis patients.Journal of neuroinflammation · 2020Review
- Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes in Cardiometabolic Diseases.Oxidative medicine and cellular longevity · 2020Review
- Prenatal epigenetics diets play protective roles against environmental pollution.Clinical epigenetics · 2019Review
- Vitamin C supplementation expands the therapeutic window of BETi for triple negative breast cancer.EBioMedicine · 2019Article
- Decreased Nuclear Ascorbate Accumulation Accompanied with Altered Genomic Methylation Pattern in Fibroblasts from Arterial Tortuosity Syndrome Patients.Oxidative medicine and cellular longevity · 2019Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Tet (ten-eleven translocation) methylcytosine dioxygenases, which belong to the iron and 2-oxoglutarate (2OG)-dependent dioxygenase superfamily, convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in DNA. We recently reported that ascorbate (vitamin C) induces Tet-mediated generation of 5hmC. To initially delineate the role of ascorbate on 5hmC generation, we analyzed whether the effect of ascorbate is dependent upon the conditions of other components involved in the hydroxylation of 5mC catalyzed by Tet. We found that removing iron from the culture medium did not affect the induction of 5hmC by ascorbate (10 μM) in mouse embryonic fibroblasts (MEFs). The effect of ascorbate did not involve an increased expression of Tet1-3 or isocitrate dehydrogenases (IDH1-2), the enzymes responsible for producing 2OG. Interestingly, MEFs cultured with different concentrations of glucose, a major precursor of 2OG, exhibited nearly identical responses to ascorbate treatment. Further, blocking the uptake of the reduced form of vitamin C, ascorbic acid, through the sodium-dependent vitamin C transporters (SVCTs) inhibited the effect of ascorbate on 5hmC. However, inhibition of the facilitative glucose transporters (GLUTs), which mediate the incorporation of the oxidized form of vitamin C, dehydroascorbic acid (DHA), did not modify the ability of ascorbate to induce 5hmC generation. These results indicate that the effect of ascorbate on 5hmC is not dependent upon iron uptake, the expression of Tet and IDH, or the production of 2OG, suggesting that ascorbate may directly participate in the generation of 5hmC, most likely as a cofactor of Tet.
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