ArticleNucleic acids research2015
Gadd45a promotes DNA demethylation through TDG.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 99 citations in OpenAlex.
- Intracellular growth ofeLife · 2026Article
- DREAMS illuminates spatial DNA and RNA modification landscapes.Nature cell biology · 2026Article
- GADD45B promotes apoptosis in intestinal ischemia/reperfusion through DNA demethylation of MST1/Hippo.Chinese medical journal · 2026Article
- The TDG protein environment connects active DNA demethylation with chromatin and RNA biology.Cellular and molecular life sciences : CMLS · 2025Article
- Interrogating subclonal heterogeneity of liver cancer with single-cell multi-omics analysis.Scientific reports · 2025Article
- LncRNAs Ride the Storm of Epigenetic Marks.Genes · 2025Review
- Influence of feeding time on daily rhythms of locomotor activity, clock genes, and epigenetic mechanisms in the liver and hypothalamus of the European sea bass (Dicentrarchus labrax).Fish physiology and biochemistry · 2025Article
- Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.Nature structural & molecular biology · 2024Article
- GADD45A regulates subcutaneous fat deposition and lipid metabolism by interacting with Stat1.BMC biology · 2023Article
- Intrapericardial long non-coding RNA-Tcf21 antisense RNA inducing demethylation administration promotes cardiac repair.European heart journal · 2023Article
- Epigenetic Regulators of DNA Cytosine Modification: Promising Targets for Cancer Therapy.Biomedicines · 2023Review
- PLEKHA4 is a novel prognostic biomarker that reshapes the tumor microenvironment in lower-grade glioma.Frontiers in immunology · 2023Article
- Levels of base excision repair proteins in CD4Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
- New Insights into TETs in Psychiatric Disorders.International journal of molecular sciences · 2022Review
- The Role of Thymine DNA Glycosylase in Transcription, Active DNA Demethylation, and Cancer.Cancers · 2022Review
- Gadd45 Proteins in Immunity 2.0.Advances in experimental medicine and biology · 2022Article
- Gadd45 in DNA Demethylation and DNA Repair.Advances in experimental medicine and biology · 2022Article
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Perturbed DNA methylation by Gadd45b induces chromatin disorganization, DNA strand breaks and dopaminergic neuron death.iScience · 2021Article
- GADD45A is a protective modifier of neurogenic skeletal muscle atrophy.JCI insight · 2021Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)-initiated oxidative demethylation. The connection of Gadd45a with oxidative demethylation is evidenced by the enhanced activation of a methylated reporter gene in HEK293T cells expressing Gadd45a in combination with catalytically active TDG and Tet. Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci most of which are also targets of TDG and show 5fC enrichment in TDG-deficient cells. These observations indicate that the demethylation effect of Gadd45a is mediated by TDG activity. This finding thus unites Gadd45a with the recently defined Tet-initiated demethylation pathway.
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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.