Hypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia

Physiological Reports

Fabiola Tros¹  Aline Meirhaeghe²  Samy Hadjadj³  Philippe Amouyel²  Pierre Bougnères¹ 

[1] INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France;INSERM, U744, Lille, France;Department of Diabetology, Poitiers Hospital, INSERM U927, INSERM CIC 802, Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France

关键词: β cells;    DNA methylation;    gene expression;    hyperglycemia;    type 2 diabetes;   

DOI  :  10.14814/phy2.12076

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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