Identification and systematic annotation of tissue-specific differentially methylated regions using the Illumina 450k array

Abstract

BackgroundDNA methylation has been recognized as a key mechanism in cell differentiation. Various studies have compared tissues to characterize epigenetically regulated genomic regions, but due to differences in study design and focus there still is no consensus as to the annotation of genomic regions predominantly involved in tissue-specific methylation. We used a new algorithm to identify and annotate tissue-specific differentially methylated regions (tDMRs) from Illumina 450k chip data for four peripheral tissues (blood, saliva, buccal swabs and hair follicles) and six internal tissues (liver, muscle, pancreas, subcutaneous fat, omentum and spleen with matched blood samples).ResultsThe majority of tDMRs, in both relative and absolute terms, occurred in CpG-poor regions. Further analysis revealed that these regions were associated with alternative transcription events (alternative first exons, mutually exclusive exons and cassette exons). Only a minority of tDMRs mapped to gene-body CpG islands (13%) or CpG islands shores (25%) suggesting a less prominent role for these regions than indicated previously. Implementation of ENCODE annotations showed enrichment of tDMRs in DNase hypersensitive sites and transcription factor binding sites. Despite the predominance of tissue differences, inter-individual differences in DNA methylation in internal tissues were correlated with those for blood for a subset of CpG sites in a locus- and tissue-specific manner.ConclusionsWe conclude that tDMRs preferentially occur in CpG-poor regions and are associated with alternative transcription. Furthermore, our data suggest the utility of creating an atlas cataloguing variably methylated regions in internal tissues that correlate to DNA methylation measured in easy accessible peripheral tissues.

Obesity is associated with depot-specific alterations in adipocyte DNA methylation and gene expression

“…13 DMRs were assigned to genes using a distance-based strategy (C/¡ 10kb of gene boundaries) as described in the methods. Comparison of DMR-associated genes revealed that the highest number of shared genes (2004) were found between inguinal and epididymal adipocytes in the DIO mice, whereas only a few of the identified DMR-associated genes were shared between adipocytes from the 2 models ( Fig.…”

Epigenome-Wide Association Study of Wellbeing

“…As described in detail by Slieker et al (2013), methylation sites were mapped to genomic features and DNase I hypersensitive sites (DHS). These genomic features consists of five gene-centric regions: (1) intergenic regions (>10 kb to -1.5 kb from the nearest transcription start site [TSS]), (2) proximal promotor (−1.5 kb to +500 kb form the nearest TSS), (3) distal promotor (−10 kb to −1.5 kb from the nearest TSS), (4) gene body (+500bp to 3 end of the gene) and (5) downstream region (3 end to +5 kb from 3 end).…”

Epigenome-Wide Association Study of Aggressive Behavior

“…Methylation sites were mapped to genomic features and DNase I hypersensitive sites (DHS) as described by Slieker et al (2013). Genomic features included five gene-centric regions: intergenic region (>10 kb from the nearest transcription start site [TSS]), distal promoter (-10 to -1.5 kb from the nearest TSS), proximal promoter (-1.5 kb to +500 bp from the nearest TSS), gene body (+500 bp to 3 end of the gene), and downstream region (3 end to +5 kb from 3 end).…”