title: Differential DNA methylation of microRNAs within promoters, intergenic and intragenic regions of type 2 diabetic, pre-diabetic and non-diabetic individuals.
abstract: OBJECTIVE
  Accumulating evidence supports the role of epigenetic modifications, and in particular DNA methylation and non-coding RNAs in the pathophysiology of type 2 diabetes. Alterations in methylation patterns within promoter regions are linked with aberrant transcription and pathological gene expression; however the role of methylation within non-promoter regions is not yet fully elucidated.
  
  
  METHODS
  We performed whole genome methylated DNA immunoprecipitation sequencing (MeDIP-Seq) in peripheral-blood-derived DNA from age-gender-body mass index (BMI)-ethnicity matched type 2 diabetic, pre-diabetic and non-diabetic individuals.
  
  
  RESULTS
  The density of methylation normalized to the average length of the promoter, intergenic and intragenic regions and to CpG count was 3.17, 9.80 and 0.09 for the promoter, intergenic and intragenic regions, respectively. Methylation within these regions varied according to glucose tolerance status and was associated with hypermethylation rather than hypomethylation. MicroRNA-DNA methylation peaks accounted for 4.8% of the total number of peaks detected. Differential DNA methylation of these microRNA peaks was observed during dysglycemia, with the promoter, intergenic and intragenic regions accounting for 2%, 95% and 3% respectively, of the differentially methylated microRNA peaks.
  
  
  CONCLUSIONS
  Genome-wide DNA methylation varied according to glucose tolerance. Methylation within non-promoter regions accounted for the majority of differentially methylated peaks identified, thus highlighting the importance of DNA methylation within these non-promoter regions in the pathogenesis of type 2 diabetes. This study suggests that DNA methylation within intergenic regions is a mechanism regulating microRNAs, another increasingly important epigenetic factor, during type 2 diabetes.
authors.affiliation: Biomedical Research and Innovation Platform, South African Medical Research Council, Cape Town, South Africa. Electronic address: carmen.pheiffer@mrc.ac.za.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pheiffer
authors.affiliation: Division of Chemical Pathology, Faculty of Medicine and Health Sciences, National Health Laboratory Service (NHLS) and University of Stellenbosch, Cape Town, South Africa; Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa.
authors.forename: Rajiv T
authors.initials: RT
authors.lastname: Erasmus
authors.affiliation: Non-Communicable Diseases Research Unit, South African Medical Research Council, Cape Town, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: Andre P
authors.initials: AP
authors.lastname: Kengne
authors.affiliation: Department of Biomedical Sciences, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, Cape Town, South Africa. Electronic address: matshat@cput.ac.za.
authors.forename: Tandi E
authors.initials: TE
authors.lastname: Matsha
mesh_terms: D016022:Case-Control Studies; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011236:Prediabetic State / Q000235:genetics*; D011401:Promoter Regions, Genetic
chemical_list: D035683:MicroRNAs
keywords: DNA methylation; Intragenic regions; MicroRNAs; Pre-diabetes; Promoters; Type 2 diabetes