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Methylation of Tcf712 promoter by high‐fat diet impairs β‐cell function in mouse pancreatic islets
Author(s) -
Hu Yun,
Shi Ping,
He Ke,
Zhu Yunqing,
Yang Fan,
Yang Min,
He BangShun,
Mao XiaoMing
Publication year - 2018
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.2980
Subject(s) - dna methylation , tcf7l2 , methylation , promoter , biology , gene expression , gene , microbiology and biotechnology , pancreatic islets , bisulfite sequencing , endocrinology , islet , diabetes mellitus , genetics , single nucleotide polymorphism , genotype
Background The TCF7L2 (transcription factor 7 like 2) gene is strongly associated with type 2 diabetes risk. However, many people without the TCF7L2 at‐risk allele develop T2D. The aim of this study was to investigate altered Tcf7l2 DNA methylation and gene expression caused by high‐fat diets (HFDs). Methods C57BL/6 mice were fed either an HFD or normal diet for 8 weeks, and intraperitoneal glucose tolerance tests were performed. Pancreatic islets were sorted for bisulfite sequencing polymerase chain reaction to determine DNA methylation status. We cloned the Tcf7l2 promoter, methylated it with methyltransferase, and transfected this construct into MIN‐6 cells to confirm the effects of promoter methylation on Tcf7l2 expression. Results Aberrant methylation at position −165 bp relative to the transcriptional start site of Tcf7l2 was present in mice fed an HFD. Accordingly, expression of Tcf7l2 mRNA and its corresponding protein was lower in the HFD group ( P < .05). Methylation of the Tcf7l2 promoter suppressed gene expression in MIN‐6 cells. Conclusion An HFD was shown to induce aberrant methylation of the Tcf7l2 promoter in mouse islets, which resulted in diminished gene expression. This study provides an evidence of the association between nutrient consumption and gene expression.