ArticleEpigenetics & chromatin2021
The DNMT1 inhibitor GSK-3484862 mediates global demethylation in murine embryonic stem cells.
Article in Epigenetics & chromatin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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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.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- Allele-specific chromatin architecture shapes imprinted domains and coordinates a distal enhancer and antisense transcription at the mouse Mest-Copg2 domain.Nature communications · 2026Article
- Gene body methylation suppresses intragenic transcription and permits epigenetic inheritance in a cnidarian.Nature ecology & evolution · 2026Article
- Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A scalable Tn5-based method for genome-wide DNA methylation profiling in development and disease.Nature communications · 2026Article
- Quantifying Epigenetic Changes Induced by Chemical Exposure Using the epi-TK Assay.Bio-protocol · 2026Article
- Flanking DNA sequences determine DNA methylation maintenance in proliferation, cancer and aging.bioRxiv : the preprint server for biology · 2026Article
- A maternal exon H splice-site variant leading to pseudohypoparathyroidism type 1B with broad methylation defects in GNAS-differentially methylated regions.Clinical epigenetics · 2026Article
- Mechanisms of gene regulation by SRCAP and H2A.Z.Nature communications · 2026Article
- Non-disruptive in vitro monitoring of cellular states with cell-free DNA methylation.Genome biology · 2026Article
- Single-molecule tracking of DNMT1 in living cells reveals its cell cycle dynamics and its redistribution upon drug treatment.Nucleic acids research · 2026Article
- Chromosome-specific epigenetic control and transmission of ribosomal DNA arrays in Hominidae genomes.Cell genomics · 2025Article
- Allelic chromatin structure is a pervasive feature of imprinted domains and functions cooperatively with cis-acting long non-coding RNAs.bioRxiv : the preprint server for biology · 2025Article
- Divergent roles of DNA methylation, TRIM28, and p53 surveillance in human embryonic and trophoblast stem cells.bioRxiv : the preprint server for biology · 2025Article
- Disrupting the epigenetic alliance: structural insights and therapeutic strategies targeting DNMT1-UHRF1.Functional & integrative genomics · 2025Review
- Article
- Exposing the DNA methylation-responsive compartment of the leukaemic genome in T-ALL cell lines support its potential as a novel therapeutic target in T-ALL.Clinical epigenetics · 2025Article
- GSK-3484862, a DNMT1 degrader, promotesNAR cancer · 2025Article
- Endocrine-disrupting chemicals (EDCs) and epigenetic regulation in embryonic development: Mechanisms, impacts, and emerging trends.Toxicology reports · 2025Review
- Dual-directional epi-genotoxicity assay for assessing chemically induced epigenetic effects utilizing the housekeeping TK gene.Scientific reports · 2025Article
- Rescuing DNMT1 fails to fully reverse the molecular and functional repercussions of its loss in mouse embryonic stem cells.Nucleic acids research · 2025Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundDNA methylation plays an important role in regulating gene expression in mammals. The covalent DNMT1 inhibitors 5-azacytidine and decitabine are widely used in research to reduce DNA methylation levels, but they impart severe cytotoxicity which limits their demethylation capability and confounds interpretation of experiments. Recently, a non-covalent inhibitor of DNMT1 called GSK-3484862 was developed by GlaxoSmithKline. We sought to determine whether GSK-3484862 can induce demethylation more effectively than 5-azanucleosides. Murine embryonic stem cells (mESCs) are an ideal cell type in which to conduct such experiments, as they have a high degree of DNA methylation but tolerate dramatic methylation loss.
resultsWe determined the cytotoxicity and optimal concentration of GSK-3484862 by treating wild-type (WT) or Dnmt1/3a/3b triple knockout (TKO) mESC with different concentrations of the compound, which was obtained from two commercial sources. Concentrations of 10 µM or below were readily tolerated for 14 days of culture. Known DNA methylation targets such as germline genes and GLN-family transposons were upregulated within 2 days of the start of GSK-3484862 treatment. By contrast, 5-azacytidine and decitabine induced weaker upregulation of methylated genes and extensive cell death. Whole-genome bisulfite sequencing showed that treatment with GSK-3484862 induced dramatic DNA methylation loss, with global CpG methylation levels falling from near 70% in WT mESC to less than 18% after 6 days of treatment with GSK-3484862. The treated cells showed a methylation level and pattern similar to that observed in Dnmt1-deficient mESCs.
conclusionsGSK-3484862 mediates striking demethylation in mESCs with minimal non-specific toxicity.
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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.