ArticleNature chemical biology2017
Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine.
Article in Nature chemical biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 85 citations in OpenAlex.
- Vitamin C boosts DNA demethylation in TET2 germline mutation carriers.Clinical epigenetics · 2023Trial
- Genomic sequence context differentially impacts stepwise oxidation by TET enzymes to shape DNA hydroxymethylation landscapes.Nucleic acids research · 2026Article
- Relationship between Prostate Cancer and Benign Hyperplasia: Role of Inflammation-Induced Oxidative Stress, Vitamin C, and Epigenetics.The world journal of men's health · 2026Review
- TET2 in epigenetic control of immune cells: Implications for inflammatory responses and age-related pathologies.The Journal of biological chemistry · 2026Review
- The role of cytosine modification symmetry in mammalian epigenome regulation.Chemical science · 2026Review
- Biochemical engineering of 5hmdC-DNA using a Tet3 double-mutant.Computational and structural biotechnology journal · 2026Article
- Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes.Stem cell reports · 2025Article
- Computational studies on the functional and structural impact of pathogenic mutations in enzymes.Protein science : a publication of the Protein Society · 2025Review
- Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Origins of Catalysis in Non-Heme Fe(II)/2-Oxoglutarate-Dependent Histone Lysine Demethylase KDM4A with Differently Methylated Histone H3 Peptides.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Epigenetic DNA modifications and vitamin C in prostate cancer and benign prostatic hyperplasia: Exploring similarities, disparities, and pathogenic implications.Neoplasia (New York, N.Y.) · 2024Article
- RNA mNature · 2024Article
- Advances in the joint profiling technologies of 5mC and 5hmC.RSC chemical biology · 2024Review
- Iterative oxidation by TET1 is required for reprogramming of imprinting control regions and patterning of mouse sperm hypomethylated regions.Developmental cell · 2024Article
- Epigenetic marks or not? The discovery of novel DNA modifications in eukaryotes.The Journal of biological chemistry · 2024Review
- The level of active DNA demethylation compounds in leukocytes and urine samples as potential epigenetic biomarkers in breast cancer patients.Scientific reports · 2024Article
- Simultaneous sequencing of genetic and epigenetic bases in DNA.Nature biotechnology · 2023Article
- 5-hydroxymethylcytosines regulate gene expression as a passive DNA demethylation resisting epigenetic mark in proliferative somatic cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- Computational Investigation of a Series of Small Molecules as Potential Compounds for Lysyl Hydroxylase-2 (LH2) Inhibition.Journal of chemical information and modeling · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Ten-eleven translocation (TET) enzymes catalyze stepwise oxidation of 5-methylcytosine (mC) to yield 5-hydroxymethylcytosine (hmC) and the rarer bases 5-formylcytosine (fC) and 5-carboxylcytosine (caC). Stepwise oxidation obscures how each individual base forms and functions in epigenetic regulation, and prompts the question of whether TET enzymes primarily serve to generate hmC or are adapted to produce fC and caC as well. By mutating a single, conserved active site residue in human TET2, Thr1372, we uncovered enzyme variants that permit oxidation to hmC but largely eliminate fC and caC. Biochemical analyses, combined with molecular dynamics simulations, elucidated an active site scaffold that is required for wild-type (WT) stepwise oxidation and that, when perturbed, explains the mutants' hmC-stalling phenotype. Our results suggest that the TET2 active site is shaped to enable higher-order oxidation and provide the first TET variants that could be used to probe the biological functions of hmC separately from fC and caC.
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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.