ArticleNucleic acids research2019
SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 76 citations in OpenAlex.
- APC coordinates GSK3 phosphorylation of SETD8 to suppress colorectal cancer.Cell reports · 2026Article
- TEffectBayes: a nextflow pipeline for exploring the potential effect of transposable elements in gene regulatory network with multi-omic Bayesian network model.Molecular genetics and genomics : MGG · 2026Article
- Discovery of a Potent, Selective, and In Vivo Efficacious Covalent Inhibitor for Lysine Methyltransferase SETD8.Journal of medicinal chemistry · 2026Article
- Review
- Machine learning-driven prediction of substrates for enzymes introducing or removing protein post-translational modifications.Communications chemistry · 2025Article
- UHRF1 and NF-κB signaling in prostate cancer progression insights from bioinformatics and experimental validation.BMC cancer · 2025Article
- SET8 modulates prognosis and radiotherapeutic efficacy by regulating radiation-induced migration in lung adenocarcinoma.Journal of translational medicine · 2025Article
- METTL21A promotes hepatocellular carcinoma progression via methylating and stabilizing BAG3.NPJ precision oncology · 2025Article
- Epigenetic regulation of neural stem cell aging in the mouse hippocampus by Setd8 downregulation.The EMBO journal · 2025Article
- Role of histone methylation in insect development: KMT5A regulates ecdysteroid biosynthesis during metamorphosis of Tribolium castaneum.Insect biochemistry and molecular biology · 2025Article
- TFProtBert: Detection of Transcription Factors Binding to Methylated DNA Using ProtBert Latent Space Representation.International journal of molecular sciences · 2025Article
- SET8 inhibition preserves PTEN to attenuate kidney cell apoptosis in cisplatin nephrotoxicity.Cell death & disease · 2025Article
- RNF4 mediated degradation of PDHA1 promotes colorectal cancer metabolism and metastasis.NPJ precision oncology · 2024Article
- Novel Insights Into DLAT's Role in Alzheimer's Disease-Related Copper Toxicity Through Microglial Exosome Dynamics.CNS neuroscience & therapeutics · 2024Article
- The scaffolding function of LSD1 controls DNA methylation in mouse ESCs.Nature communications · 2024Article
- Antitumorigenic potential of Lactobacillus-derived extracellular vesicles: p53 succinylation and glycolytic reprogramming in intestinal epithelial cells via SIRT5 modulation.Cell biology and toxicology · 2024Article
- WSB1/2 target chromatin-bound lysine-methylated RelA for proteasomal degradation and NF-κB termination.Nucleic acids research · 2024Article
- DNMT1-targeting remodeling global DNA hypomethylation for enhanced tumor suppression and circumvented toxicity in oral squamous cell carcinoma.Molecular cancer · 2024Article
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
- Substrate and Functional Diversity of Protein Lysine Post-translational Modifications.Genomics, proteomics & bioinformatics · 2024Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Faithful inheritance of DNA methylation across cell division requires DNMT1 and its accessory factor UHRF1. However, how this axis is regulated to ensure DNA methylation homeostasis remains poorly understood. Here we show that SET8, a cell-cycle-regulated protein methyltransferase, controls protein stability of both UHRF1 and DNMT1 through methylation-mediated, ubiquitin-dependent degradation and consequently prevents excessive DNA methylation. SET8 methylates UHRF1 at lysine 385 and this modification leads to ubiquitination and degradation of UHRF1. In contrast, LSD1 stabilizes both UHRF1 and DNMT1 by demethylation. Importantly, SET8 and LSD1 oppositely regulate global DNA methylation and do so most likely through regulating the level of UHRF1 than DNMT1. Finally, we show that UHRF1 downregulation in G2/M by SET8 has a role in suppressing DNMT1-mediated methylation on post-replicated DNA. Altogether, our study reveals a novel role of SET8 in promoting DNA methylation homeostasis and identifies UHRF1 as the hub for tuning DNA methylation through dynamic protein methylation.
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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.