ArticleScientific reports2016
Dioxin induces Ahr-dependent robust DNA demethylation of the Cyp1a1 promoter via Tdg in the mouse liver.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Epigenetic mechanisms linking the perinatal environment, the placenta, and maternal and child health outcomes: evidence for sexual dimorphism.Environmental epigenetics · 2026Article
- Exploring the link between environmental chemical exposures and epigenetic modifications in diabetes mellitus: A review.Biomolecules & biomedicine · 2025Review
- An epigenetic memory at the CYP1A gene in cancer-resistant, pollution-adapted killifish.Scientific reports · 2025Article
- New insights into coordinated regulation of AHR promoter transcription; molecular mechanisms and therapeutic targets.International journal of biological sciences · 2025Review
- An epigenetic memory at thebioRxiv : the preprint server for biology · 2024Article
- Costs of molecular adaptation to the chemical exposome: a focus on xenobiotic metabolism pathways.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- The complex biology of aryl hydrocarbon receptor activation in cancer and beyond.Biochemical pharmacology · 2023Review
- The Aryl Hydrocarbon Receptor, Epigenetics and the Aging Process.The journal of nutrition, health & aging · 2023Article
- Mono-(2-ethyl-5-hydroxyhexyl) phthalate promotes uterine leiomyoma cell survival through tryptophan-kynurenine-AHR pathway activation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology.Journal of molecular endocrinology · 2022Review
- Exposure to 3,3',4,4',5-Pentachlorobiphenyl (PCB126) Causes Widespread DNA Hypomethylation in Adult Zebrafish Testis.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- A perspective on persistent toxicants in veterans and amyotrophic lateral sclerosis: identifying exposures determining higher ALS risk.Journal of neurology · 2022Review
- The roles of inducible chromatin and transcriptional memory in cellular defense system responses to redox-active pollutants.Free radical biology & medicine · 2021Review
- Tumour Microenvironment: Roles of the Aryl Hydrocarbon Receptor, O-GlcNAcylation, Acetyl-CoA and Melatonergic Pathway in Regulating Dynamic Metabolic Interactions across Cell Types-Tumour Microenvironment and Metabolism.International journal of molecular sciences · 2020Review
- Ascorbic acid during the suckling period is required for proper DNA demethylation in the liver.Scientific reports · 2020Article
- Dioxin Disrupts Dynamic DNA Methylation Patterns in Genes That Govern Cardiomyocyte Maturation.Toxicological sciences : an official journal of the Society of Toxicology · 2020Article
- 6-Prenylnaringenin from Hops Disrupts ERα-Mediated Downregulation ofChemical research in toxicology · 2020Article
- Epigenetic Regulations of AhR in the Aspect of Immunomodulation.International journal of molecular sciences · 2020Review
- Differential methylation pattern of xenobiotic metabolizing genes and susceptibility to Balkan endemic nephropathy, in a cohort of Romanian patients.Journal of nephrology · 2020Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1). A single dose of TCDD administered to adult mice induced Ahr-dependent CpG hypomethylation, changes in histone modifications, and thymine DNA glycosylase (Tdg) recruitment at the Cyp1a1 promoter in the liver within 24 hrs. These epigenetic changes persisted until 40 days post-TCDD treatment and there was Cyp1a1 mRNA hyperinduction upon repeat administration of TCDD at this time-point. Our demethylation assay using siRNA knockdown and an in vitro methylated plasmid showed that Ahr, Tdg, and the ten-eleven translocation methyldioxygenases Tet2 and Tet3 are required for the TCDD-induced DNA demethylation. These results provide novel evidence of Ahr-driven active DNA demethylation and epigenetic memory. The epigenetic alterations influence response to subsequent chemical exposure and imply an adaptive mechanism to xenobiotic stress.
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