%0 Journal Article %1 yamaguchi2024noncanonical %A Yamaguchi, Kosuke %A Chen, Xiaoying %A Rodgers, Brianna %A Miura, Fumihito %A Bashtrykov, Pavel %A Bonhomme, Frédéric %A Salinas-Luypaert, Catalina %A Haxholli, Deis %A Gutekunst, Nicole %A Aygenli, Bihter Özdemir %A Ferry, Laure %A Kirsh, Olivier %A Laisné, Marthe %A Scelfo, Andrea %A Ugur, Enes %A Arimondo, Paola B %A Leonhardt, Heinrich %A Kanemaki, Masato T %A Bartke, Till %A Fachinetti, Daniele %A Jeltsch, Albert %A Ito, Takashi %A Defossez, Pierre-Antoine %C England %D 2024 %J Nature communications %K ajeltsch ibtb-bc imported myown unibibliografie %N 1 %P 2960--2960 %R 10.1038/s41467-024-47314-4 %T Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells %U https://pubmed.ncbi.nlm.nih.gov/38580649 %V 15 %X 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.

@article{yamaguchi2024noncanonical, 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.}, added-at = {2024-04-12T10:06:16.000+0200}, address = {England}, author = {Yamaguchi, Kosuke and Chen, Xiaoying and Rodgers, Brianna and Miura, Fumihito and Bashtrykov, Pavel and Bonhomme, Frédéric and Salinas-Luypaert, Catalina and Haxholli, Deis and Gutekunst, Nicole and Aygenli, Bihter Özdemir and Ferry, Laure and Kirsh, Olivier and Laisné, Marthe and Scelfo, Andrea and Ugur, Enes and Arimondo, Paola B and Leonhardt, Heinrich and Kanemaki, Masato T and Bartke, Till and Fachinetti, Daniele and Jeltsch, Albert and Ito, Takashi and Defossez, Pierre-Antoine}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/280c1dad5e21fe1072e6cc71b42faec62/ajeltsch}, comment = {38580649[pmid] PMC10997609[pmcid]}, description = {Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells - PubMed}, doi = {10.1038/s41467-024-47314-4}, interhash = {22d6a648b21e7440823c1f66d04f11b9}, intrahash = {80c1dad5e21fe1072e6cc71b42faec62}, issn = {20411723}, journal = {Nature communications}, keywords = {ajeltsch ibtb-bc imported myown unibibliografie}, month = apr, number = 1, pages = {2960--2960}, timestamp = {2024-04-12T10:06:16.000+0200}, title = {Non-canonical functions of UHRF1 maintain DNA methylation homeostasis in cancer cells}, url = {https://pubmed.ncbi.nlm.nih.gov/38580649}, volume = 15, year = 2024 }