Reference - Detail
| RRC ID | 78733 |
|---|---|
| Author | Yamaguchi K, Chen X, Rodgers B, Miura F, Bashtrykov P, Bonhomme F, Salinas-Luypaert C, Haxholli D, Gutekunst N, Aygenli BÖ, Ferry L, Kirsh O, Laisné M, Scelfo A, Ugur E, Arimondo PB, Leonhardt H, Kanemaki MT, Bartke T, Fachinetti D, Jeltsch A, Ito T, Defossez PA. |
| Title | Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells. |
| Journal | Nat Commun |
| Abstract |
DNA methylation is an essential epigenetic chromatin modification, and its maintenance in mammals requires the protein UHRF1. It is yet unclear if UHRF1 functions solely by stimulating DNA methylation maintenance by DNMT1, or if it has important additional functions. Using degron alleles, we show that UHRF1 depletion causes a much greater loss of DNA methylation than DNMT1 depletion. This is not caused by passive demethylation as UHRF1-depleted cells proliferate more slowly than DNMT1-depleted cells. Instead, bioinformatics, proteomics and genetics experiments establish that UHRF1, besides activating DNMT1, interacts with DNMT3A and DNMT3B and promotes their activity. In addition, we show that UHRF1 antagonizes active DNA demethylation by TET2. Therefore, UHRF1 has non-canonical roles that contribute importantly to DNA methylation homeostasis; these findings have practical implications for epigenetics in health and disease. |
| Volume | 15(1) |
| Pages | 2960 |
| Published | 2024-4-5 |
| DOI | 10.1038/s41467-024-47314-4 |
| PII | 10.1038/s41467-024-47314-4 |
| PMID | 38580649 |
| PMC | PMC10997609 |
| MeSH | Animals CCAAT-Enhancer-Binding Proteins / genetics CCAAT-Enhancer-Binding Proteins / metabolism Chromatin DNA (Cytosine-5-)-Methyltransferase 1 / genetics DNA (Cytosine-5-)-Methyltransferase 1 / metabolism DNA (Cytosine-5-)-Methyltransferases / genetics DNA (Cytosine-5-)-Methyltransferases / metabolism DNA Methylation* Mammals / genetics Neoplasms* / genetics Ubiquitin-Protein Ligases / genetics Ubiquitin-Protein Ligases / metabolism |
| IF | 12.121 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 30 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | HCT116 Tet-OsTIR1(RCB4663) |