Open AccessHypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia
Author(s) -
Tros Fabiola,
Meirhaeghe Aline,
Hadjadj Samy,
Amouyel Philippe,
Bougnères Pierre,
Fradin Delphine
Publication year - 2014
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12076
Subject(s) - epigenetics , dna methylation , epigenome , differentially methylated regions , biology , methylation , gene expression , bisulfite sequencing , gene , microbiology and biotechnology , regulation of gene expression , promoter , bisulfite , genetics
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 BTC 3 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 ( DMR s), 14 were associated with changes in gene expression, suggesting an epigenetic effect of high glucose on gene transcription at these loci. Among these 14 DMR s, we selected for further study Pp2ac , a gene previously suspected to play a role in β ‐cell physiology and type 2 diabetes. Using RT‐q PCR and bisulfite pyrosequencing, we confirmed our previous observations in BTC 3 cells and found that this gene was significantly demethylated in the whole blood cells (WBCs) of type 2 diabetic patients compared to controls.