Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells.

Autor: Yamaguchi K; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France. yamako0801@icloud.com., Chen X; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France., Rodgers B; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France., Miura F; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Bashtrykov P; Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Stuttgart, Germany., Bonhomme F; Institut Pasteur, Université Paris Cité, Epigenetic Chemical Biology, CNRS, UMR 3523, Chem4Life, Paris, France., Salinas-Luypaert C; Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France., Haxholli D; Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, Germany., Gutekunst N; Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Stuttgart, Germany., Aygenli BÖ; Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg, Germany., Ferry L; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France., Kirsh O; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France., Laisné M; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France., Scelfo A; Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France., Ugur E; Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, Germany., Arimondo PB; Institut Pasteur, Université Paris Cité, Epigenetic Chemical Biology, CNRS, UMR 3523, Chem4Life, Paris, France., Leonhardt H; Faculty of Biology and Center for Molecular Biosystems (BioSysM), Human Biology and BioImaging, Ludwig-Maximilians-Universität München, Munich, Germany., Kanemaki MT; Department of Chromosome Science, National Institute of Genetics, Research Organization of Information and Systems (ROIS), Mishima, Shizuoka, Japan.; Graduate Institute for Advanced Studies, SOKENDAI, Mishima, Shizuoka, Japan.; Department of Biological Science, The University of Tokyo, Bunkyo-ku, Tokyo, Japan., Bartke T; Institute of Functional Epigenetics, Helmholtz Zentrum München, Neuherberg, Germany., Fachinetti D; Institut Curie, PSL Research University, CNRS, UMR 144, Paris, France., Jeltsch A; Institute of Biochemistry and Technical Biochemistry, Department of Biochemistry, University of Stuttgart, Stuttgart, Germany., Ito T; Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan., Defossez PA; Université Paris Cité, CNRS, Epigenetics and Cell Fate, Paris, France. pierre-antoine.defossez@cnrs.fr.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 05; Vol. 15 (1), pp. 2960. Date of Electronic Publication: 2024 Apr 05.
DOI: 10.1038/s41467-024-47314-4
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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