ArticleMolecular cell2025
DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states.
Article in Molecular cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- The Role of Epigenetics in Corneal Fibrosis.Epigenomes · 2026Review
- Article
- Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Histone modification cross-talk: analytical tools and molecular mechanisms.The Biochemical journal · 2026Review
- UHRF1 drives subtype-independent aggressiveness and immune evasion in small cell lung cancer through PRC2 interactions.iScience · 2026Article
- Hat1 Orchestrates Heterochromatin Inheritance by Regulating Localization of H3K9 Methyltransferases.bioRxiv : the preprint server for biology · 2026Article
- UHRF1 as an epigenetic therapeutic target in Cancer.Molecular biology reports · 2026Review
- Preliminary Evidence of Blood DNA Methylation Changes in Pregnant Women Adhering to a Mediterranean Diet.Epigenomes · 2026Article
- KDM3B promotes neural invasion in colorectal cancer through TrkA upregulation by inhibiting H3K9 dimethylation.iScience · 2025Article
- H3K36 Methylation as a Guardian of Epigenome Integrity.Nature communications · 2025Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- Endurance training increases a ubiquitylated form of histone H3 in the skeletal muscle, supporting Notch1 upregulation in an MDM2-dependent manner.The Journal of physiology · 2025Article
- Dual EZH1/2 inhibition enhances DNMT inhibitor efficacy in colon cancer through targeting H3K27me1.bioRxiv : the preprint server for biology · 2025Article
- The Dual Role ofBiology · 2025Review
- Disrupting the epigenetic alliance: structural insights and therapeutic strategies targeting DNMT1-UHRF1.Functional & integrative genomics · 2025Review
- Discovery and Characterization of Uracil Derivatives Targeting the Set-and-Ring Domain of UHRF1.Journal of chemical information and modeling · 2025Article
- The SWI/SNF-related protein SMARCA3 is a histone H3K23 ubiquitin ligase that regulates H3K9me3 in cancer.Molecular cell · 2025Article
- Dynamic modifications of circular RNAs drive oncogenesis.Epigenomics · 2025Review
- UHRF1 in Immune Regulation and Diseases: Mechanisms and Therapeutic Implications.Clinical reviews in allergy & immunology · 2025Review
- Mechanistic insights into the stimulation of the histone H3K9 methyltransferase Clr4 by proximal H3K14 ubiquitination.Science advances · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
Mono-ubiquitination of lysine 18 on histone H3 (H3K18ub), catalyzed by UHRF1, is a DNMT1 docking site that facilitates replication-coupled DNA methylation maintenance. Its functions beyond this are unknown. Here, we genomically map simultaneous increases in UHRF1-dependent H3K18ub and SUV39H1/H2-dependent H3K9me3 following DNMT1 inhibition. Mechanistically, transient accumulation of hemi-methylated DNA at CpG islands facilitates UHRF1 recruitment and E3 ligase activity toward H3K18. Notably, H3K18ub enhances SUV39H1/H2 methyltransferase activity and, in colon cancer cells, nucleates new H3K9me3 domains at CpG island promoters of DNA methylation-silenced tumor suppressor genes (TSGs). Disrupting UHRF1 enzyme activity prevents H3K9me3 accumulation while promoting PRC2-dependent H3K27me3 as a tertiary layer of gene repression in these regions. By contrast, disrupting H3K18ub-dependent SUV39H1/H2 activity enhances the transcriptional activating and antiproliferative effects of DNMT1 inhibition. Collectively, these findings reveal roles for UHRF1 and H3K18ub in regulating a hierarchy of repressive histone methylation signaling and rationalize a combination strategy for epigenetic cancer therapy.
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