ArticleCell discovery2016
Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer.
Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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
49 citing papers in PubMed, 95 citations in OpenAlex.
- Mapping genetic modifiers of epimutation rates identifies VIM2/4 as dosage-sensitive negative regulators of CG methylation maintenance.Nature plants · 2026Article
- Hypomethylation of FAM83A in lung adenocarcinoma mirrors an epigenetic signature of airway cell differentiation states.Discover oncology · 2026Article
- The prognostic value of ubiquitin/ubiquitin-like-related genes along with immune cell infiltration and clinicopathological features in osteosarcoma.Journal of orthopaedic surgery and research · 2024Article
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- Epigenome-850K-wide profiling reveals peripheral blood differential methylation in term low birth weight.Epigenomics · 2024Article
- Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors.Cells · 2023Article
- Epigenetics Mechanisms of Honeybees: Secrets of Royal Jelly.Epigenetics insights · 2023Review
- Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation.Nature communications · 2022Article
- Comprehensive Analysis of Acquired Genetic Variants and Their Prognostic Impact in Systemic Mastocytosis.Cancers · 2022Review
- Large-Scale Chromatin Rearrangements in Cancer.Cancers · 2022Review
- UHRF2 regulates cell cycle, epigenetics and gene expression to control the timing of retinal progenitor and ganglion cell differentiation.Development (Cambridge, England) · 2022Article
- DNMT1 regulates the timing of DNA methylation by DNMT3 in an enzymatic activity-dependent manner in mouse embryonic stem cells.PloS one · 2022Article
- UHRF1: a novel metabolic guardian restricting AMPK activity.Cell research · 2022Article
- Nuclear UHRF1 is a gate-keeper of cellular AMPK activity and function.Cell research · 2022Article
- FAK Activation Promotes SMC Dedifferentiation via Increased DNA Methylation in Contractile Genes.Circulation research · 2021Article
- Article
- Staying true to yourself: mechanisms of DNA methylation maintenance in mammals.Nucleic acids research · 2021Review
- F-box protein CFK1 interacts with and degrades de novo DNA methyltransferase in Arabidopsis.The New phytologist · 2021Article
- UHRF1 Is a Novel Druggable Epigenetic Target in Malignant Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2021Article
- DNA methylation in Hepatoblastoma-a literature review.Italian journal of pediatrics · 2020Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Global DNA hypomethylation is a most common epigenetic alteration in cancer, but the mechanism remains elusive. Previous studies demonstrate that UHRF1 but not UHRF2 is required for mediating DNA maintenance methylation by DNMT1. Here we report unexpectedly a conserved function for UHRF1 and UHRF2: inhibiting de novo DNA methylation by functioning as E3 ligases promoting DNMT3A degradation. UHRF1/2 are frequently overexpressed in cancers and we present evidence that UHRF1/2 overexpression downregulates DNMT3A proteins and consequently leads to DNA hypomethylation. Abrogating this negative regulation on DNMT3A or overexpression of DNMT3A leads to increased DNA methylation and impaired tumor growth. We propose a working model that UHRF1/2 safeguards the fidelity of DNA methylation and suggests that UHRF1/2 overexpression is likely a causal factor for widespread DNA hypomethylation in cancer via suppressing DNMT3A.
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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.