The histone demethylase Phf2 acts as a ...
Type de document :
Article dans une revue scientifique
PMID :
URL permanente :
Titre :
The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity.
Auteur(s) :
Bricambert, Julien [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Alves-Guerra, Marie-Clotilde [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Esteves, Pauline [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Prip-Buus, Carina [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Bertrand-Michel, Justine [Auteur]
Guillou, Herve [Auteur]
Chang Christopher, J [Auteur]
Vander Wal Mark, N [Auteur]
Canonne-Hergaux, Francois [Auteur]
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Raverdy, Violeta [Auteur]
Université Lille Nord (France)
Pattou, Francois [Auteur]
Université Lille Nord (France)
Girard, Jean [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Postic, Catherine [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Dentin, Renaud [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Alves-Guerra, Marie-Clotilde [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Esteves, Pauline [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Prip-Buus, Carina [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Bertrand-Michel, Justine [Auteur]
Guillou, Herve [Auteur]
Chang Christopher, J [Auteur]
Vander Wal Mark, N [Auteur]
Canonne-Hergaux, Francois [Auteur]
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Raverdy, Violeta [Auteur]
Université Lille Nord (France)
Pattou, Francois [Auteur]
Université Lille Nord (France)
Girard, Jean [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Postic, Catherine [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Dentin, Renaud [Auteur]
Institut Cochin [IC UM3 (UMR 8104 / U1016)]
Titre de la revue :
Nature Communications
Nom court de la revue :
Nat. Commun.
Numéro :
9
Date de publication :
2018
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains ...
Lire la suite >Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD.Lire moins >
Lire la suite >Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD.Lire moins >
Langue :
Anglais
Audience :
Internationale
Vulgarisation :
Non
Établissement(s) :
Inserm
Université de Lille
CHU Lille
Université de Lille
CHU Lille
Collections :
Équipe(s) de recherche :
Inflammatory digestive disease : pathophysiology and therapeutic targets developement
Date de dépôt :
2019-03-01T14:08:07Z
2021-06-22T07:45:36Z
2023-12-05T14:18:27Z
2021-06-22T07:45:36Z
2023-12-05T14:18:27Z
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