دورية أكاديمية
Tunable DNMT1 degradation reveals DNMT1/DNMT3B synergy in DNA methylation and genome organization
| العنوان: | Tunable DNMT1 degradation reveals DNMT1/DNMT3B synergy in DNA methylation and genome organization |
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| المؤلفون: | Scelfo, Andrea, Barra, Viviana, Abdennur, Nezar, Spracklin, George, Busato, Florence, Salinas-Luypaert, Catalina, Bonaiti, Elena, Velasco, Guillaume, Bonhomme, Frédéric, Chipont, Anna, Tijhuis, Andréa E, Spierings, Diana C J, Guérin, Coralie, Arimondo, Paola, Francastel, Claire, Foijer, Floris, Tost, Jӧrg, Mirny, Leonid, Fachinetti, Daniele |
| المساهمون: | Genomics and Computational Biology, Program in Bioinformatics and Integrative Biology, Systems Biology |
| المصدر: | The Journal of cell biology ; 223 ; 4 ; United States |
| سنة النشر: | 2024 |
| المجموعة: | University of Massachusetts, Medical School: eScholarship@UMMS |
| مصطلحات موضوعية: | Chromatin or epigenetics, Genetics |
| الوصف: | DNA methylation (DNAme) is a key epigenetic mark that regulates critical biological processes maintaining overall genome stability. Given its pleiotropic function, studies of DNAme dynamics are crucial, but currently available tools to interfere with DNAme have limitations and major cytotoxic side effects. Here, we present cell models that allow inducible and reversible DNAme modulation through DNMT1 depletion. By dynamically assessing whole genome and locus-specific effects of induced passive demethylation through cell divisions, we reveal a cooperative activity between DNMT1 and DNMT3B, but not of DNMT3A, to maintain and control DNAme. We show that gradual loss of DNAme is accompanied by progressive and reversible changes in heterochromatin, compartmentalization, and peripheral localization. DNA methylation loss coincides with a gradual reduction of cell fitness due to G1 arrest, with minor levels of mitotic failure. Altogether, this system allows DNMTs and DNA methylation studies with fine temporal resolution, which may help to reveal the etiologic link between DNAme dysfunction and human disease. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1540-8140 |
| العلاقة: | Journal of Cell Biology; https://doi.org/10.1083/jcb.202307026Test; Scelfo A, Barra V, Abdennur N, Spracklin G, Busato F, Salinas-Luypaert C, Bonaiti E, Velasco G, Bonhomme F, Chipont A, Tijhuis AE, Spierings DCJ, Guérin C, Arimondo P, Francastel C, Foijer F, Tost J, Mirny L, Fachinetti D. Tunable DNMT1 degradation reveals DNMT1/DNMT3B synergy in DNA methylation and genome organization. J Cell Biol. 2024 Apr 1;223(4):e202307026. doi:10.1083/jcb.202307026. Epub 2024 Feb 20. PMID: 38376465; PMCID: PMC10876481.; http://hdl.handle.net/20.500.14038/53272Test; The Journal of cell biology |
| DOI: | 10.1083/jcb.202307026 |
| الإتاحة: | https://doi.org/10.1083/jcb.202307026Test https://doi.org/20.500.14038/53272Test https://hdl.handle.net/20.500.14038/53272Test |
| حقوق: | © 2024 Scelfo et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/termsTest/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0Test/). ; Attribution-NonCommercial-ShareAlike 4.0 International ; http://creativecommons.org/licenses/by-nc-sa/4.0Test/ |
| رقم الانضمام: | edsbas.EE5BC564 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 15408140 |
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| DOI: | 10.1083/jcb.202307026 |