biostudies-literaturePedrotti SItalian Ministry of HealthFSH SocietyMarie Curie Individual FellowshipEPIGENERA-Net for Research on Rare DiseasesItalian Association for Cancer ResearchFSHD Global Research Foundationeaav1472https://www.ebi.ac.uk/biostudies/studies/S-EPMC6469946biostudies-literatureUnknown5(4)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 proteinScience advancesThe Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.PMC6469946EASY-746974AIRC under IG 2017 – ID 19919de Palma CGiovarelli MPedrotti SGarcia-Manteiga JMRaso MEsposito ANeguembor MVCanu TClementi EDoglioni CMolineris ICaccia RFiocchi AFerri GGabellini DMarra PSanvito FfalseThe Suv420h histone methyltransferases regulate PPAR-γ and energy expenditure in response to environmental stimuli.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 protein2019-01-01T00:00:00Z2019 Apr2026-05-05T02:56:59.043Z2019-06-06T21:12:00ZS-EPMC64699463100158110.1126/sciadv.aav1472