ArticleCell research2011
S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance.
Article in Cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 135 citations in OpenAlex.
- Dynamic regulation of H3K9 modifications in cancer: pathogenesis and targeted therapies.Biomarker research · 2026Review
- Mammalian DNA maintenance methylation depends on histone but not PAF15 ubiquitination.Nature communications · 2026Article
- Functional characterization of UHRF1 variants in facilitating DNA methylation.The Journal of biological chemistry · 2026Article
- 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
- Reversing transgene silencing via targeted chromatin editing.bioRxiv : the preprint server for biology · 2025Article
- Decoding the base flipping mechanism of the SET- and RING-associated (SRA) domain of the epigenetic UHRF1 protein.Nucleic acids research · 2025Article
- UHRF2 mediates resistance to DNA methylation reprogramming in primordial germ cells.Nature communications · 2025Article
- The Role of the DNA Methyltransferase Family and the Therapeutic Potential of DNMT Inhibitors in Tumor Treatment.Current oncology (Toronto, Ont.) · 2025Review
- Single-cell sequencing in non-obstructive azoospermia: insights from primary and re-analysis studies.Frontiers in endocrinology · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Roles of post-translational modifications of UHRF1 in cancer.Epigenetics & chromatin · 2024Review
- Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.Nature communications · 2024Article
- UHRF2 accumulates in early GCell cycle (Georgetown, Tex.) · 2024Article
- Transcriptome signatures of host tissue infected with African swine fever virus reveal differential expression of associated oncogenes.Archives of virology · 2024Review
- Mechanistic insights into UHRF1‑mediated DNA methylation by structure‑based functional clarification of UHRF1 domains (Review).Oncology letters · 2023Review
- Single-cell multi-omics sequencing of human spermatogenesis reveals a DNA demethylation event associated with male meiotic recombination.Nature cell biology · 2023Article
- Impaired Repopulating Ability ofGenes · 2023Article
- Methylation is maintained specifically at imprinting control regions but not other DMRs associated with imprinted genes in mice bearing a mutation in theFrontiers in cell and developmental biology · 2023Article
- Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia.Cancers · 2022Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1. UHRF2, another member of the UHRF family proteins, is highly similar to UHRF1 in both sequence and structure, raising questions about its role in DNA methylation. In this study, we demonstrate that, like UHRF1, UHRF2 also binds preferentially to methylated histone H3 lysine 9 (H3K9) through its conserved tudor domain and hemi-methylated DNA through the SET and Ring associated domain. Like UHRF1, UHRF2 is enriched in pericentric heterochromatin. The heterochromatin localization depends to large extent on its methylated H3K9-binding activity and to less extent on its methylated DNA-binding activity. Coimmunoprecipitation experiments demonstrate that both UHRF1 and UHRF2 interact with DNMT1, DNMT3a, DNMT3b and G9a. Despite all these conserved functions, we find that UHRF2 is not able to rescue the DNA methylation defect in Uhrf1 null mouse embryonic stem cells. This can be attributed to the inability for UHRF2 to recruit DNMT1 to replication foci during S phase of the cell cycle. Indeed, we find that while UHRF1 interacts with DNMT1 in an S phase-dependent manner in cells, UHRF2 does not. Thus, our study demonstrates that UHRF2 and UHRF1 are not functionally redundant in DNA methylation maintenance and reveals the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation.
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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.