ArticleEnvironmental science & technology2015
Arsenite Targets the Zinc Finger Domains of Tet Proteins and Inhibits Tet-Mediated Oxidation of 5-Methylcytosine.
Article in Environmental science & technology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 53 citations in OpenAlex.
- Integration of epigenetics into ecotoxicology: insights and fundamental research needs.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Arsenic induced Hippo pathway dysregulation linked to hTERT hypo-methylation in breast cancer patients.Frontiers in epigenetics and epigenomics · 2026Article
- Epigenetics: A link between toxicants and diseases.iScience · 2025Review
- Environmental Exposure, Epitranscriptomic Perturbations, and Human Diseases.Environmental science & technology · 2025Review
- Changes in Energy Dynamics in Arsenic Exposure based Neurotoxicity: A Comprehensive Review.Current medicinal chemistry · 2025Review
- Activated fibroblasts modify keratinocyte stem niche through TET1 and IL-6 to promote their rapid transformation in a mouse model of prenatal arsenic exposure.Scientific reports · 2024Article
- Epigenomic reprogramming in iAs-mediated carcinogenesis.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Article
- Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome.Chemical research in toxicology · 2022Article
- Review
- Arsenic exposure and human blood DNA methylation and hydroxymethylation profiles in two diverse populations from Bangladesh and Spain.Environmental research · 2022Article
- Arsenic-induced epigenetic changes in cancer development.Seminars in cancer biology · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Does Arsenic Contamination Affect DNA Methylation Patterns in a Wild Bird Population? An Experimental Approach.Environmental science & technology · 2021Article
- Arsenite Binds to ZNF598 to Perturb Ribosome-Associated Protein Quality Control.Chemical research in toxicology · 2020Article
- Environmental Epigenetics and Genome Flexibility: Focus on 5-Hydroxymethylcytosine.International journal of molecular sciences · 2020Review
- Molecular Mechanisms of Arsenic-Induced Disruption of DNA Repair.Chemical research in toxicology · 2020Review
- Decreased global DNA hydroxymethylation in neural tube defects: Association with polycyclic aromatic hydrocarbons.Epigenetics · 2019Article
- Arsenite Targets the RING Finger Domain of Rbx1 E3 Ubiquitin Ligase to Inhibit Proteasome-Mediated Degradation of Nrf2.Chemical research in toxicology · 2018Article
- Arsenite Binds to the Zinc Finger Motif of TIP60 Histone Acetyltransferase and Induces Its Degradation via the 26S Proteasome.Chemical research in toxicology · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Arsenic toxicity is a serious public health problem worldwide that brings more than 100 million people into the risk of arsenic exposure from groundwater and food contamination. Although there is accumulating evidence linking arsenic exposure with aberrant cytosine methylation in the global genome or at specific genomic loci, very few have investigated the impact of arsenic on the oxidation of 5-methylcytosine (5-mC) mediated by the Ten-eleven translocation (Tet) family of proteins. Owing to the high binding affinity of As(III) toward cysteine residues, we reasoned that the highly conserved C3H-type zinc fingers situated in Tet proteins may constitute potential targets for arsenic binding. Herein, we found that arsenite could bind directly to the zinc fingers of Tet proteins in vitro and in cells, and this interaction substantially impaired the catalytic efficiency of Tet proteins in oxidizing 5-mC to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Treatments with arsenite also led to a dose-dependent decrease in the level of 5-hmC, but not 5-mC, in DNA isolated from HEK293T cells overexpressing the catalytic domain of any of the three Tet proteins and from mouse embryonic stem cells. Together, our study unveiled, for the first time, that arsenite could alter epigenetic signaling by targeting the zinc fingers of Tet proteins and perturbing the Tet-mediated oxidation of 5-mC in vitro and in cells. Our results offer important mechanistic understanding of arsenic epigenotoxicity and carcinogenesis in mammalian systems and may lead to novel approaches for the chemoprevention of arsenic toxicity.
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