ArticleMolecular cell2018
A Bifunctional Role for the UHRF1 UBL Domain in the Control of Hemi-methylated DNA-Dependent Histone Ubiquitylation.
Article in Molecular cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 84 citations in OpenAlex.
- Gene regulatory mechanisms downstream of DNA methylation.Nature reviews. Genetics · 2026Review
- Cytoplasmic lattices store developmentally poised degradative and cytoskeletal complexes in mammalian eggs.Nature structural & molecular biology · 2026Article
- In-situ cryo-ET of mouse embryos reveals cytoplasmic lattices contain ubiquitin-charged E2-E3 ligase assemblies.The EMBO journal · 2026Article
- Synthesis and characterization of a novel phosphatidylinositol 5-phosphate (PI(5)P) photoaffinity probe.RSC chemical biology · 2026Article
- Functional characterization of UHRF1 variants in facilitating DNA methylation.The Journal of biological chemistry · 2026Article
- Article
- NLRP14 modulates the activity of E3 ubiquitin ligases during the oocyte-to-embryo transition.Nature communications · 2026Article
- The cytoplasmic lattice in mammalian eggs sequesters ubiquitination machinery and tubulin in reserve.bioRxiv : the preprint server for biology · 2026Article
- A role of protein conformational dynamics in mammalian DNA methylation.Structural dynamics (Melville, N.Y.) · 2026Review
- Linked-domain inhibitors designed to block UBE2D induce the unfolded protein response.Cell chemical biology · 2025Article
- UHRF1 Controls the Timing of RAD51 Removal During DNA Damage Repair Through Suppressing RFWD3.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Germline variants inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- UHRF1 promotes epithelial-mesenchymal transition mediating renal fibrosis by activating the TGF-β/SMAD signaling pathway.Scientific reports · 2025Article
- DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states.Molecular cell · 2025Article
- Chemical Tools for Probing the Ub/Ubl Conjugation Cascades.Chembiochem : a European journal of chemical biology · 2025Review
- UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.Nucleic acids research · 2024Article
- Design of linked-domain protein inhibitors of UBE2D as tools to study cellular ubiquitination.bioRxiv : the preprint server for biology · 2024Article
- Oncogenic Roles of UHRF1 in Cancer.Epigenomes · 2024Review
- Structure of human DPPA3 bound to the UHRF1 PHD finger reveals its functional and structural differences from mouse DPPA3.Communications biology · 2024Article
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
DNA methylation patterns regulate gene expression programs and are maintained through a highly coordinated process orchestrated by the RING E3 ubiquitin ligase UHRF1. UHRF1 controls DNA methylation inheritance by reading epigenetic modifications to histones and DNA to activate histone H3 ubiquitylation. Here, we find that all five domains of UHRF1, including the previously uncharacterized ubiquitin-like domain (UBL), cooperate for hemi-methylated DNA-dependent H3 ubiquitin ligation. Our structural and biochemical studies, including mutations found in cancer genomes, reveal a bifunctional requirement for the UBL in histone modification: (1) the UBL makes an essential interaction with the backside of the E2 and (2) the UBL coordinates with other UHRF1 domains that recognize epigenetic marks on DNA and histone H3 to direct ubiquitin to H3. Finally, we show UBLs from other E3s also have a conserved interaction with the E2, Ube2D, highlighting a potential prevalence of interactions between UBLs and E2s.
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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.