ArticleProceedings of the National Academy of Sciences of the United States of America2016
Retinol and ascorbate drive erasure of epigenetic memory and enhance reprogramming to naïve pluripotency by complementary mechanisms.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
What it found
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Who cites it
98 citing papers in PubMed, 163 citations in OpenAlex.
- Oral vitamin C supplementation to patients with myeloid cancer on azacitidine treatment: Normalization of plasma vitamin C induces epigenetic changes.Clinical epigenetics · 2019Trial
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- Dynamic control of cell state transitions during tissue morphogenesis.The EMBO journal · 2026Review
- Beyond redox: vitamin C in signaling, epigenetic regulation and protein modification-relevance to cancer therapy.Clinical epigenetics · 2026Review
- Vitamin a modulates neurogenesis-associated pathways and cholinergic signaling in Alzheimer's disease: potential role of reactive astrocytes via NGN2/SOX-11 and SIRT-1.Scientific reports · 2026Article
- Vitamin C Conditioning Generates Tumor-Targeting CAR T Cells with Superior Cytotoxicity and Fitness in a Posttransplant Lymphoproliferative Disorder Tumor Model.Molecular cancer therapeutics · 2026Article
- Retinoic acid and ascorbate synergize to suppress myeloid leukemia via TET2 activation.Cell reports · 2025Article
- Epi-nutrients for cancer prevention: Molecular mechanisms and emerging insights.Cell biology and toxicology · 2025Review
- Cell identity and 5-hydroxymethylcytosine.Epigenetics & chromatin · 2025Review
- The physiological functions of ascorbate in the development of cancer.Disease models & mechanisms · 2025Review
- Exploring the Ascorbate Requirement of the 2-Oxoglutarate-Dependent Dioxygenases.Journal of medicinal chemistry · 2025Review
- Tet3-mediated DNA demethylation is essential for maintaining the dedifferentiation capacity of mammalian Müller glia.Frontiers in molecular neuroscience · 2025Article
- Unravelling the role of TET2 in venous thromboembolism: insights into mechanisms and therapeutic implications.Frontiers in cardiovascular medicine · 2025Review
- Oxidative stress-mediated apoptosis via theFrontiers in pediatrics · 2025Article
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- The interferon γ pathway enhances pluripotency and X-chromosome reactivation in iPSC reprogramming.Science advances · 2024Article
- Ultrasensitive detection of 5-hydroxymethylcytosine in genomic DNA using a graphene-based sensor modified with biotin and gold nanoparticles.Materials today. Bio · 2024Article
- Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?Cellular and molecular life sciences : CMLS · 2024Review
- Using NMR to Monitor TET-Dependent Methylcytosine Dioxygenase Activity and Regulation.ACS chemical biology · 2024Article
- Micronutrient regulation of the DNA methylome.Frontiers in epigenetics and epigenomics · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 4 countries.
Funding
Abstract
Epigenetic memory, in particular DNA methylation, is established during development in differentiating cells and must be erased to create naïve (induced) pluripotent stem cells. The ten-eleven translocation (TET) enzymes can catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidized derivatives, thereby actively removing this memory. Nevertheless, the mechanism by which the TET enzymes are regulated, and the extent to which they can be manipulated, are poorly understood. Here we report that retinoic acid (RA) or retinol (vitamin A) and ascorbate (vitamin C) act as modulators of TET levels and activity. RA or retinol enhances 5hmC production in naïve embryonic stem cells by activation of TET2 and TET3 transcription, whereas ascorbate potentiates TET activity and 5hmC production through enhanced Fe
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.