ArticleNucleic acids research2018
Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 44 citations in OpenAlex.
- E3 ligase UHRF2 hijacks nuclear TBK1 to epigenetically repress type I interferons expression.International journal of biological sciences · 2026Article
- UHRF2 as a genetic correlate of hospitalization in sickle cell disease.British journal of haematology · 2025Article
- UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells.Nature communications · 2025Article
- UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.Nucleic acids research · 2024Article
- 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 Methylation Machinery in Gastropod Mollusks.Life (Basel, Switzerland) · 2024Review
- UHRF2 accumulates in early GCell cycle (Georgetown, Tex.) · 2024Article
- Enhanced Transcriptional Signature and Expression of Histone-Modifying Enzymes in Salivary Gland Tumors.Cells · 2023Article
- Dppa3 facilitates self-renewal of embryonic stem cells by stabilization of pluripotent factors.Stem cell research & therapy · 2022Article
- UHRF2 regulates cell cycle, epigenetics and gene expression to control the timing of retinal progenitor and ganglion cell differentiation.Development (Cambridge, England) · 2022Article
- Biology of PEST-Containing Nuclear Protein: A Potential Molecular Target for Cancer Research.Frontiers in oncology · 2022Review
- RNA Sequencing Analysis of Gene Expression by Electroacupuncture in Guinea Pig Gallstone Models.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- An Overview of Epigenetic Methylation in Pancreatic Cancer Progression.Frontiers in oncology · 2022Review
- Proteins That Read DNA Methylation.Advances in experimental medicine and biology · 2022Article
- A trivalent nucleosome interaction by PHIP/BRWD2 is disrupted in neurodevelopmental disorders and cancer.Genes & development · 2021Article
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
- TETology: Epigenetic Mastermind in Action.Applied biochemistry and biotechnology · 2021Review
- Chromatin Regulation through Ubiquitin and Ubiquitin-like Histone Modifications.Trends in biochemical sciences · 2021Review
- The histone and non-histone methyllysine reader activities of the UHRF1 tandem Tudor domain are dispensable for the propagation of aberrant DNA methylation patterning in cancer cells.Epigenetics & chromatin · 2020Article
- The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation.The Journal of biological chemistry · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
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Abstract
UHRF1 is a histone- and DNA-binding E3 ubiquitin ligase that functions with DNMT1 to maintain mammalian DNA methylation. UHRF1 facilitates DNMT1 recruitment to replicating chromatin through a coordinated mechanism involving histone and DNA recognition and histone ubiquitination. UHRF2 shares structural homology with UHRF1, but surprisingly lacks functional redundancy to facilitate DNA methylation maintenance. Molecular mechanisms uncoupling UHRF2 from DNA methylation maintenance are poorly defined. Through comprehensive and comparative biochemical analysis of recombinant human UHRF1 and UHRF2 reader and writer activities, we reveal conserved modes of histone PTM recognition but divergent DNA binding properties. While UHRF1 and UHRF2 diverge in their affinities toward hemi-methylated DNA, we surprisingly show that both hemi-methylated and hemi-hydroxymethylated DNA oligonucleotides stimulate UHRF2 ubiquitin ligase activity toward histone H3 peptide substrates. This is the first example of an E3 ligase allosterically regulated by DNA hydroxymethylation. However, UHRF2 is not a productive histone E3 ligase toward purified mononucleosomes, suggesting UHRF2 has an intra-domain architecture distinct from UHRF1 that is conformationally constrained when bound to chromatin. Collectively, our studies reveal that uncoupling of UHRF2 from the DNA methylation maintenance program is linked to differences in the molecular readout of chromatin signatures that connect UHRF1 to ubiquitination of histone H3.
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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.