ArticleProceedings of the National Academy of Sciences of the United States of America2018
Chromatin structure and its chemical modifications regulate the ubiquitin ligase substrate selectivity of UHRF1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 56 citations in OpenAlex.
- Disruption of the SAGA CORE triggers collateral degradation of KAT2A.Nature communications · 2026Article
- UHRF1 as an epigenetic therapeutic target in Cancer.Molecular biology reports · 2026Review
- Nucleosome context regulates chromatin reader preference.Nucleic acids research · 2025Article
- The SWI/SNF-related protein SMARCA3 is a histone H3K23 ubiquitin ligase that regulates H3K9me3 in cancer.Molecular cell · 2025Article
- Proteomic-based stemness score measures oncogenic dedifferentiation and enables the identification of druggable targets.Cell genomics · 2025Article
- DNA hypomethylation promotes UHRF1-and SUV39H1/H2-dependent crosstalk between H3K18ub and H3K9me3 to reinforce heterochromatin states.Molecular cell · 2025Article
- UHRF1 ubiquitin ligase activity supports the maintenance of low-density CpG methylation.Nucleic acids research · 2024Article
- CDCA7 is an evolutionarily conserved hemimethylated DNA sensor in eukaryotes.Science advances · 2024Article
- Natural and Synthetic Anticancer Epidrugs Targeting the Epigenetic Integrator UHRF1.Molecules (Basel, Switzerland) · 2023Review
- GSK-3484862 targets DNMT1 for degradation in cells.NAR cancer · 2023Article
- Mechanisms of chromatin-based epigenetic inheritance.Science China. Life sciences · 2022Review
- Locally correlated kinetics of post-replication DNA methylation reveals processivity and region specificity in DNA methylation maintenance.Journal of the Royal Society, Interface · 2022Article
- H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination.Science China. Life sciences · 2022Article
- Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1.Biochemistry · 2022Article
- Interplay between chromatin marks in development and disease.Nature reviews. Genetics · 2022Review
- The multi-functionality of UHRF1: epigenome maintenance and preservation of genome integrity.Nucleic acids research · 2021Review
- The interplay between DNA and histone methylation: molecular mechanisms and disease implications.EMBO reports · 2021Review
- Staying true to yourself: mechanisms of DNA methylation maintenance in mammals.Nucleic acids research · 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
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Mitotic inheritance of DNA methylation patterns is facilitated by UHRF1, a DNA- and histone-binding E3 ubiquitin ligase that helps recruit the maintenance DNA methyltransferase DNMT1 to replicating chromatin. The DNA methylation maintenance function of UHRF1 is dependent on its ability to bind chromatin, where it facilitates monoubiquitination of histone H3 at lysines 18 and 23, a docking site for DNMT1. Because of technical limitations, this model of UHRF1-dependent DNA methylation inheritance has been constructed largely based on genetics and biochemical observations querying methylated DNA oligonucleotides, synthetic histone peptides, and heterogeneous chromatin extracted from cells. Here, we construct semisynthetic mononucleosomes harboring defined histone and DNA modifications and perform rigorous analysis of UHRF1 binding and enzymatic activity with these reagents. We show that multivalent engagement of nucleosomal linker DNA and dimethylated lysine 9 on histone H3 directs UHRF1 ubiquitin ligase activity toward histone substrates. Notably, we reveal a molecular switch, stimulated by recognition of hemimethylated DNA, which redirects UHRF1 ubiquitin ligase activity away from histones in favor of robust autoubiquitination. Our studies support a noncompetitive model for UHRF1 and DNMT1 chromatin recruitment to replicating chromatin and define a role for hemimethylated linker DNA as a regulator of UHRF1 ubiquitin ligase substrate selectivity.
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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.