ArticleNature2016
Tumour hypoxia causes DNA hypermethylation by reducing TET activity.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 347 papers, 1 of them a synthesis that pooled it.
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Who cites it
347 citing papers in PubMed, 1 synthesis or guideline pooled it, 656 citations in OpenAlex.
- Maternal iron status in early pregnancy and DNA methylation in offspring: an epigenome-wide meta-analysis.Clinical epigenetics · 2022Pooled it
- Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Addressing the Limits of Emx2 Therapy of Glioblastoma Multiforme by Transgene Insulation and Epigenetic Pharmacological Intervention.Biomedicines · 2026Article
- Biomolecular Condensates Integrate Transcriptional and Epigenetic Responses to Hypoxia.International journal of molecular sciences · 2026Review
- Inaccurate interpretation of hypoxia signatures from transcriptomic analyses in neuro-oncology.Neoplasia (New York, N.Y.) · 2026Review
- Oxygenaging: A Physiological Framework for Geroscience.Aging cell · 2026Review
- Increasing TET Expression and 5-Hydroxymethylcytosine Formation by a Carbocyclic 5-Aza-2'-deoxy-cytidine Antimetabolite.Angewandte Chemie (International ed. in English) · 2026Article
- Loss of TET2 sulfhydration results in destabilization of TET2 and down-regulation of the immune response in melanoma.Acta pharmaceutica Sinica. B · 2026Article
- Impact of mitochondrial reductive stress due to respiratory chain limitation on cancer via posttranslational modifications.Redox biology · 2026Review
- Gliomas with succinate dehydrogenase deficiency: A case series and brief review of the literature of oncometabolite-driven gliomagenesis.Journal of neuropathology and experimental neurology · 2026Review
- Epigenetic vulnerability in endocrine disruption: bridging mechanisms, models, and environmental inequities.Clinical epigenetics · 2026Review
- Hypoxia Associated Integration of Epigenetic, Metabolic, and Immune Biomarkers in Blood and Urine for Early Colorectal Cancer Detection: A Multimarker Panel.Diagnostics (Basel, Switzerland) · 2026Article
- The Complex Role of Methylation in Regulating Vascular Smooth Muscle Cell Phenotypic States in Vascular Remodeling and Atherosclerosis.Biomolecules · 2026Review
- Single-cell and deep learning identify hypoxia-responsive lncRNAs predicting outcomes in colorectal cancer.NPJ precision oncology · 2026Article
- Time-dependent memory of hypoxia exposure influences tumor invasion dynamics.bioRxiv : the preprint server for biology · 2026Article
- Hypoxia Promotes an Adrenergic to Mesenchymal Transcriptional Program Transition in Neuroblastoma.Clinical and translational science · 2026Article
- DNA methyltransferase inhibition is a therapeutic vulnerability in VHL-deficient renal cell carcinoma cells.Experimental & molecular medicine · 2026Article
- Epigenetic modulation to overcome immune suppression in pancreatic cancer.Clinical epigenetics · 2026Review
- Hypoxia Signaling and Non-Coding RNAs: Regulatory Networks and Therapeutic Implications in Breast Cancer.Current issues in molecular biology · 2026Review
- Genome-wide DNA methylation changes after 24 hours at high altitude.Environmental epigenetics · 2026Article
287 more citing papers are in PubMed but not listed here.
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19 authors at 5 institutions in 4 countries.
Funding
Abstract
Hypermethylation of the promoters of tumour suppressor genes represses transcription of these genes, conferring growth advantages to cancer cells. How these changes arise is poorly understood. Here we show that the activity of oxygen-dependent ten-eleven translocation (TET) enzymes is reduced by tumour hypoxia in human and mouse cells. TET enzymes catalyse DNA demethylation through 5-methylcytosine oxidation. This reduction in activity occurs independently of hypoxia-associated alterations in TET expression, proliferation, metabolism, hypoxia-inducible factor activity or reactive oxygen species, and depends directly on oxygen shortage. Hypoxia-induced loss of TET activity increases hypermethylation at gene promoters in vitro. In patients, tumour suppressor gene promoters are markedly more methylated in hypoxic tumour tissue, independent of proliferation, stromal cell infiltration and tumour characteristics. Our data suggest that up to half of hypermethylation events are due to hypoxia, with these events conferring a selective advantage. Accordingly, increased hypoxia in mouse breast tumours increases hypermethylation, while restoration of tumour oxygenation abrogates this effect. Tumour hypoxia therefore acts as a novel regulator of DNA methylation.
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Registered trials
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.