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

Authors

  • Fabiola Tros,

    1. INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France
    Current affiliation:
    1. UMR1002, Paris, France
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  • Aline Meirhaeghe,

    1. INSERM, U744, Lille, France
    2. Institut Pasteur de Lille, Université Lille Nord de France, Lille, France
    3. UDSL, Lille, France
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  • Samy Hadjadj,

    1. Department of Diabetology, Poitiers Hospital, INSERM U927, INSERM CIC 802, Université de Poitiers, UFR Médecine Pharmacie, Poitiers, France
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  • Philippe Amouyel,

    1. INSERM, U744, Lille, France
    2. Institut Pasteur de Lille, Université Lille Nord de France, Lille, France
    3. UDSL, Lille, France
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  • Pierre Bougnères,

    1. INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France
    2. Department of Pediatric Endocrinology, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France
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  • Delphine Fradin

    Corresponding author
    1. INSERM U986, Bicêtre Hospital, Paris Sud University, Le Kremlin-Bicêtre, France
    • Correspondence

      Delphine Fradin, INSERM U986, 78 avenue du Général Leclerc, 94276 Le Kremlin-Bicêtre, France.

      Tel: + 33 1 49 59 53 86

      Fax: + 33 1 49 59 19 59

      E-mail: delphine.fradin@inserm.fr

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  • Funding Information

    This work was supported by the Association pour la Recherche sur le Diabète (ARD) and by the DIM “Cardiovasculaire, obésité, rein et diabète” (Post-doctoral grant 2011).

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.

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