title: Hypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia.
abstract: In order to identify epigenetic mechanisms through which hyperglycemia can affect gene expression durably in β cells, we screened DNA methylation changes induced by high glucose concentrations (25 mmol/L) in the BTC3 murine cell line, using an epigenome-wide approach. Exposure of BTC3 cells to high glucose modified the expression of 1612 transcripts while inducing significant methylation changes in 173 regions. Among these 173 glucose-sensitive differentially methylated regions (DMRs), 14 were associated with changes in gene expression, suggesting an epigenetic effect of high glucose on gene transcription at these loci. Among these 14 DMRs, we selected for further study Pp2ac, a gene previously suspected to play a role in β-cell physiology and type 2 diabetes. Using RT-qPCR and bisulfite pyrosequencing, we confirmed our previous observations in BTC3 cells and found that this gene was significantly demethylated in the whole blood cells (WBCs) of type 2 diabetic patients compared to controls.
authors.affiliation: INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France UMR1002, Paris, France.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Tros
authors.affiliation: INSERM, U744, Lille, France Institut Pasteur de Lille, Université Lille Nord de France, Lille, France UDSL, Lille, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Meirhaeghe
authors.affiliation: Department of Diabetology, Poitiers Hospital, INSERM U927, INSERM CIC 802, Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.affiliation: INSERM, U744, Lille, France Institut Pasteur de Lille, Université Lille Nord de France, Lille, France UDSL, Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Amouyel
authors.affiliation: INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Bougnères
authors.affiliation: INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Fradin
keywords: DNA methylation; gene expression; hyperglycemia; type 2 diabetes; β cells