論文 - 詳細
| RRC ID | 78733 |
|---|---|
| 著者 | 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. |
| タイトル | Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells. |
| ジャーナル | 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. |
| 巻・号 | 15(1) |
| ページ | 2960 |
| 公開日 | 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 30 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HCT116 Tet-OsTIR1(RCB4663) |