Bioinformatics analysis of abnormal DNA methylation in muscle samples from monozygotic twins discordant for type 2 diabetes

Abstract

Abstract. The present study aimed to examine the changes in DNA methylation of gene promoters associated with type 2 diabetes (T2D). The DNA methylation profile dataset GSE38291 was downloaded from the Gene Expression Omnibus database. A paired t-test was used to analyze differences in the DNA methylation of gene promoters between T2D and normal muscle samples. Gene Ontology (GO) enrichment analysis was performed using online tool, The Database for Annotation, Visualization and Integrated Discovery. Whole-Genome rVISTA was used to analyze the enriched transcription factor (TF) binding sites upstream of the transcription start site in the differentially methylated genes. A total of 38 genes, including Sirtuin 1, N-acetyltransferase 6, phospholipase A2 group XIIB and nuclear factor of activated T cells calcineurin-dependent 1, were identified to be differentially methylated between these two groups. One GO term, DNA geometric change (GO:0032392), was significantly enriched (P<0.05) by the hyper-methylated genes. In addition, the binding sites of one gene, zinc finger E-box binding homeobox 1, and three TFs, methyl CpG binding protein 2, TFEB and TFAP4, were significantly enriched in the hyper-and hypo-methylated genes, respectively. The resulting T2D-associated genes and potential TFs provided a novel insight into the molecular mechanisms underlying the pathology of T2D. These genes may become promising target genes for the development of treatments for T2D.

Epigenetic modifications in pancreas development, diabetes, and therapeutics

“…In another study, when the DNA methylation profile dataset GSE38291, downloaded from the Gene Expression Omnibus database, was examined for changes in DNA methylation of gene promoters associated with T2D by GO analysis, a total of 38 genes (e.g., SIRT1 , N‐acetyltransferase 6 [ NAT6 ], phospholipase A2 group XIIB [ PLA2G12B ], and nuclear factor of activated T cells calcineurin‐dependent 1 [ NFATC1 ]) were identified to be differentially methylated between the muscles of T2D and control samples. Analysis of transcription factor binding sites for the methylation changes revealed that the binding sites of zinc finger E‐box binding homeobox 1 ( ZEB1 ) were hypermethylated, whereas the binding sites of three TFs (methyl CpG binding protein 2 [MECP2], TFEB, and TFAP4) were significantly hypomethylated 129 …”

“…Analysis of transcription factor binding sites for the methylation changes revealed that the binding sites of zinc finger E‐box binding homeobox 1 ( ZEB1 ) were hypermethylated, whereas the binding sites of three TFs (methyl CpG binding protein 2 [MECP2], TFEB, and TFAP4) were significantly hypomethylated. 129 …”

Identical Twins Doubly Exchanged at Birth: A Case Report of Genetic and Environmental Influences on the Adult Epigenome

“…Epigenetics describes a number of biological processes whereby gene expression is regulated and maintained through cell division and includes the addition of small mole cules such as the methyl group (CH 3 ) to DNA and its packaging proteins. Recently, epigenetic analyses of disease-discordant MZ twins have drawn attention to mechanisms relevant to the differential expression of relevant genes [5,6], barring the presence of rare postzygotic mutation [7]. DNA methylation at the dinucleotide CpG is an epigenetic mechanism which is often associated with repression of gene expression.…”