ArticleGenome biology2021
Roles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells.
Article in Genome biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
- TET2 as a Context-Dependent Epigenetic Integrator in Clonal Hematopoiesis, Inflammation, Cancer, and Immunotherapy.Cell biochemistry and function · 2026Review
- Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers.Nature chemical biology · 2026Article
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- Article
- A distinct subclade of AlkB family demethylases in ciliates safeguards the positional fidelity of eukaryotic NProceedings of the National Academy of Sciences of the United States of America · 2026Article
- TDG orchestrates ATF4-dependent gene transcription during retinoic acid-induced cell fate acquisition.Nucleic acids research · 2026Article
- Mbd4 and MutSα protect cells from spontaneous deamination of 5-methylcytosine.Nucleic acids research · 2026Article
- Triphenyl phosphate induces coordinated DNA methylation and gene expression changes in aquatic embryonic cells.Environmental epigenetics · 2026Article
- Involvement of the DNA Demethylase Thymine DNA Glycosylase in Anticancer Drug Resistance.Biomolecules & therapeutics · 2025Article
- Dietary iron attenuates epigenetic aging through DNA methylation remodeling and extends survival in older adults.Clinical epigenetics · 2025Article
- Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes.Stem cell reports · 2025Article
- Vector-free intra-airway in vivo epigenetic editing.Trends in biotechnology · 2025Article
- TET1: The epigenetic architect of clinical disease progression.Genes & diseases · 2025Review
- Identification of m5C-related genes and subclusters in recurrent pregnancy loss.Journal of assisted reproduction and genetics · 2025Article
- Review
- Mechanism of cytarabine-induced neurotoxicity.Nature · 2025Article
- Temporally discordant chromatin accessibility and DNA demethylation define short- and long-term enhancer regulation during cell fate specification.Cell reports · 2025Article
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- Landscape of TET2 Mutations: From Hematological Malignancies to Solid Tumors.Cancer medicine · 2025Review
- A mutant ASXL1-BAP1-EHMT complex contributes to heterochromatin dysfunction in clonal hematopoiesis and chronic monomyelocytic leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundTET enzymes mediate DNA demethylation by oxidizing 5-methylcytosine (5mC) in DNA to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Since these oxidized methylcytosines (oxi-mCs) are not recognized by the maintenance methyltransferase DNMT1, DNA demethylation can occur through "passive," replication-dependent dilution when cells divide. A distinct, replication-independent ("active") mechanism of DNA demethylation involves excision of 5fC and 5caC by the DNA repair enzyme thymine DNA glycosylase (TDG), followed by base excision repair.
resultsHere by analyzing inducible gene-disrupted mice, we show that DNA demethylation during primary T cell differentiation occurs mainly through passive replication-dependent dilution of all three oxi-mCs, with only a negligible contribution from TDG. In addition, by pyridine borane sequencing (PB-seq), a simple recently developed method that directly maps 5fC/5caC at single-base resolution, we detect the accumulation of 5fC/5caC in TDG-deleted T cells. We also quantify the occurrence of concordant demethylation within and near enhancer regions in the Il4 locus. In an independent system that does not involve cell division, macrophages treated with liposaccharide accumulate 5hmC at enhancers and show altered gene expression without DNA demethylation; loss of TET enzymes disrupts gene expression, but loss of TDG has no effect. We also observe that mice with long-term (1 year) deletion of Tdg are healthy and show normal survival and hematopoiesis.
conclusionsWe have quantified the relative contributions of TET and TDG to cell differentiation and DNA demethylation at representative loci in proliferating T cells. We find that TET enzymes regulate T cell differentiation and DNA demethylation primarily through passive dilution of oxi-mCs. In contrast, while we observe a low level of active, replication-independent DNA demethylation mediated by TDG, this process does not appear to be essential for immune cell activation or differentiation.
Indexed as
Identifiers
What OpenQuestion holds
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.