The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli

Pedrotti, Simona; Caccia, Roberta; Neguembor, Maria Victoria; García Manteiga, José Manuel; Ferri, Giulia; Palma, Clara de; Canu, Tamara; Giovarelli, Matteo; Marra, Paolo; Fiocchi, Amleto; Molineris, Ivan; Raso, Michele; Sanvito, Francesca; Doglioni, Claudio; Esposito, Antonio; Clementi, Emilio; Gabellini, Davide

The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli

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dc.contributor.author Pedrotti, Simona
dc.contributor.author Caccia, Roberta
dc.contributor.author Neguembor, Maria Victoria
dc.contributor.author García Manteiga, José Manuel
dc.contributor.author Ferri, Giulia
dc.contributor.author Palma, Clara de
dc.contributor.author Canu, Tamara
dc.contributor.author Giovarelli, Matteo
dc.contributor.author Marra, Paolo
dc.contributor.author Fiocchi, Amleto
dc.contributor.author Molineris, Ivan
dc.contributor.author Raso, Michele
dc.contributor.author Sanvito, Francesca
dc.contributor.author Doglioni, Claudio
dc.contributor.author Esposito, Antonio
dc.contributor.author Clementi, Emilio
dc.contributor.author Gabellini, Davide
dc.date.accessioned 2020-04-07T08:48:04Z
dc.date.available 2020-04-07T08:48:04Z
dc.date.issued 2019
dc.description.abstract Obesity and its associated metabolic abnormalities have become a global emergency with considerable morbidity and mortality. Epidemiologic and animal model data suggest an epigenetic contribution to obesity. Nevertheless, the cellular and molecular mechanisms through which epigenetics contributes to the development of obesity remain to be elucidated. Suv420h1 and Suv420h2 are histone methyltransferases responsible for chromatin compaction and gene repression. Through in vivo, ex vivo, and in vitro studies, we found that Suv420h1 and Suv420h2 respond to environmental stimuli and regulate metabolism by down-regulating peroxisome proliferator-activated receptor gamma (PPAR-γ), a master transcriptional regulator of lipid storage and glucose metabolism. Accordingly, mice lacking Suv420h proteins activate PPAR-γ target genes in brown adipose tissue to increase mitochondria respiration, improve glucose tolerance, and reduce adipose tissue to fight obesity. We conclude that Suv420h proteins are key epigenetic regulators of PPAR-γ and the pathways controlling metabolism and weight balance in response to environmental stimuli.
dc.description.sponsorship Work in the Gabellini laboratory was supported by the Italian Epigenomics Flagship Project (EPIGEN), the FSHD Global Research Foundation, the ERA-Net for Research on Rare Diseases, the FSH Society, the Italian Ministry of Health, and the Italian Association for Cancer Research (AIRC under IG 2017—ID 19919). S.P. was supported by a Marie Curie Individual Fellowship (EASY-746974). This work was also supported by the Italian Ministry of Health with 5 × 1000 funds. Funding bodies had no role in the design of the study; in the collection, analysis, and interpretation of data; and in the writing of the manuscript.
dc.format.mimetype application/pdf
dc.identifier.citation Pedrotti S, Caccia R, Neguembor MV, Garcia-Manteiga JM, Ferri G, de Palma C, Canu T, Giovarelli M, Marra P, Fiocchi A, Molineris I, Raso M, Sanvito F, Doglioni C, Esposito A, Clementi E, Gabellini D. The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli. Sci Adv. 2019; 5(4):eaav1472. DOI: 10.1126/sciadv.aav1472
dc.identifier.doi http://dx.doi.org/10.1126/sciadv.aav1472
dc.identifier.issn 2375-2548
dc.identifier.uri http://hdl.handle.net/10230/44180
dc.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Sci Adv. 2019; 5(4):eaav1472
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/646974
dc.rights © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title The Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/publishedVersion

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