ArticleNature2011
Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability.
Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 213 papers.
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Who cites it
213 citing papers in PubMed, 386 citations in OpenAlex.
- Abasic site repair in APE1-deficient mouse embryonic stem cells: a matter for the MRN complex and ATM signaling.Nucleic acids research · 2026Article
- Targeting transcriptional plasticity in cancer.Nature chemical biology · 2026Article
- Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers.Nature chemical biology · 2026Article
- PARP1 inhibition in naïve mouse embryonic stem cells induces viral mimicry.Nucleic acids research · 2026Article
- Thymine DNA glycosylase binds to R-loops and excises 5-formyl and 5-carboxyl cytosine from DNA/RNA hybrids.The Journal of biological chemistry · 2026Article
- A founder heterozygous mutation in methyl-CpG binding domain protein 4 (MBD4) prevalent among Israeli Christian Arabs predisposes to increased mutagenesis.Haematologica · 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
- 8-Oxoguanine: A Lesion, an Epigenetic Mark, or a Molecular Signal?International journal of molecular sciences · 2025Review
- What is in a name? Rethinking SMUG1 in genome maintenance.NAR cancer · 2025Review
- The TDG protein environment connects active DNA demethylation with chromatin and RNA biology.Cellular and molecular life sciences : CMLS · 2025Article
- Establishment of neuronal and glial competence of neural stem cells requires distinct enzymatic activities of TET enzymes.Stem cell reports · 2025Article
- Zebrafish Unga Is Required for Genomic Maintenance upon Genotoxic Stress and Male Fertility.Journal of developmental biology · 2025Article
- Identification of m5C-related genes and subclusters in recurrent pregnancy loss.Journal of assisted reproduction and genetics · 2025Article
- Mechanisms underlying low mutation rates in mammalian oocytes and preimplantation embryos.Nucleic acids research · 2025Review
- Chemical Switching: A Concept Inspired by Strategies from Biocatalysis and Organocatalysis.Chembiochem : a European journal of chemical biology · 2025Review
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- A Balancing Act: Thymine DNA Glycosylase Combines Sequence and Rotational Preferences To Define Lesion Excision in the Nucleosome Core Particle.Biochemistry · 2025Article
- Article
- Thymine DNA glycosylase combines sliding, hopping, and nucleosome interactions to efficiently search for 5-formylcytosine.Nature communications · 2024Article
153 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thymine DNA glycosylase (TDG) is a member of the uracil DNA glycosylase (UDG) superfamily of DNA repair enzymes. Owing to its ability to excise thymine when mispaired with guanine, it was proposed to act against the mutability of 5-methylcytosine (5-mC) deamination in mammalian DNA. However, TDG was also found to interact with transcription factors, histone acetyltransferases and de novo DNA methyltransferases, and it has been associated with DNA demethylation in gene promoters following activation of transcription, altogether implicating an engagement in gene regulation rather than DNA repair. Here we use a mouse genetic approach to determine the biological function of this multifaceted DNA repair enzyme. We find that, unlike other DNA glycosylases, TDG is essential for embryonic development, and that this phenotype is associated with epigenetic aberrations affecting the expression of developmental genes. Fibroblasts derived from Tdg null embryos (mouse embryonic fibroblasts, MEFs) show impaired gene regulation, coincident with imbalanced histone modification and CpG methylation at promoters of affected genes. TDG associates with the promoters of such genes both in fibroblasts and in embryonic stem cells (ESCs), but epigenetic aberrations only appear upon cell lineage commitment. We show that TDG contributes to the maintenance of active and bivalent chromatin throughout cell differentiation, facilitating a proper assembly of chromatin-modifying complexes and initiating base excision repair to counter aberrant de novo methylation. We thus conclude that TDG-dependent DNA repair has evolved to provide epigenetic stability in lineage committed cells.
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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.