Sistema de Salut de Catalunya
Institut Català de la Salut
[Sayago C, Sánchez-Wandelmer J, García F] Proteomics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Hurtado B] Cell Division and Cancer Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Cancer Cell Cycle group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Lafarga V] Genomic Instability Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. [Prieto P] Mouse Genome Editing Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
Vall d'Hebron Barcelona Hospital Campus
2023-06-19T07:33:12Z
2023-06-19T07:33:12Z
2023-05-25
Methylation; Proteomics
Metilació; Proteòmica
Metilación; Proteómica
Protein methylation is an important modification beyond epigenetics. However, systems analyses of protein methylation lag behind compared to other modifications. Recently, thermal stability analyses have been developed which provide a proxy of a protein functional status. Here, we show that molecular and functional events closely linked to protein methylation can be revealed by the analysis of thermal stability. Using mouse embryonic stem cells as a model, we show that Prmt5 regulates mRNA binding proteins that are enriched in intrinsically disordered regions and involved in liquid-liquid phase separation mechanisms, including the formation of stress granules. Moreover, we reveal a non-canonical function of Ezh2 in mitotic chromosomes and the perichromosomal layer, and identify Mki67 as a putative Ezh2 substrate. Our approach provides an opportunity to systematically explore protein methylation function and represents a rich resource for understanding its role in pluripotency.
We thank all members of the CNIO Proteomics Unit for discussions, the CNIO Flow Cytometry Unit for flow cytometry support, Cyan Lynch for sharing reagents and Ana Martinez-Val for support with data analysis. This work was supported by SAF2016-74962-R (MINECO) and the European Union Horizon 2020 program INFRAIA project EPIC-XS (project 823839). The CNIO Proteomics Unit belongs to ProteoRed, PRB3- ISCIII, supported by grant PT17/0019/0005. J.M. is supported by the Ikerbasque Programme, Basque Foundation for Science. O.F-C. is supported by grants from the Spanish Ministry of Science, Innovation and Universities (PID2021-128722OB-I00, co-financed with European FEDER funds) and the Spanish Association Against Cancer (AECC; PROYE20101FERN). M.M. lab was supported by grants from MINECO (PID2021-128726 and PDC2022-133408-I00), and Comunidad de Madrid (Y2020/BIO-6519 and S2022/BMD-7437).
Article
Published version
English
Metilació; Ratolins; Cèl·lules mare embrionàries; Epigènesi; PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic; ANATOMY::Cells::Stem Cells::Pluripotent Stem Cells::Embryonic Stem Cells::Mouse Embryonic Stem Cells; PHENOMENA AND PROCESSES::Chemical Phenomena::Biochemical Phenomena::Alkylation::Methylation; FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética; ANATOMÍA::células::células madre::células madre pluripotentes::células madre embrionarias::células madre embrionarias del ratón; FENÓMENOS Y PROCESOS::fenómenos químicos::fenómenos bioquímicos::alquilación::metilación
Nature Portfolio
Nature Communications;14
https://doi.org/10.1038/s41467-023-38863-1
info:eu-repo/grantAgreement/EC/H2020/823839
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
