Unknown,Transcriptomics,Genomics,Proteomics

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Global DNA methylation landscape reveals roles of DNA methylation involved in the regulation of drug metabolizing enzyme [II]

ABSTRACT: In order to elucidate the role of DNA methylation in the DME gene regulation, global DNA methylation and mRNA expression profiles of human tissues and cell lines were examinde by HumanMethylation450 Bead Chip and SurePrint G3 Human Gene Expression 8×60K v2. We demonstrated DNA methylation landscape of the DME genes in human tissues. Although a fraction of DME genes can be regulated by their DNA methylation, the variable DNA methylation status probably affects drug metabolism and response. Bisulphite converted DNA from the 7 samples were hybridized to the Illumina HumanMethylation450 BeadChip.

ORGANISM(S): Homo sapiens

SUBMITTER: Wataru Habano

PROVIDER: E-GEOD-67477 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Low birth weight is associated with an increased adult metabolic disease risk. It is widely discussed that poor intrauterine conditions could induce long-lasting epigenetic modifications, leading to systemic changes in regulation of metabolic genes. In a unique cohort of 17 monozygotic (MZ) monochorionic female twins very discordant for birth weight (relative differences ranging from 21.3-35.7%), we examined if adverse prenatal growth conditions experienced by the smaller co-twins lead to systemic long-lasting DNA methylation changes. Genome-wide DNA methylation profiles were acquired from saliva DNA using the Infinium HumanMethylation450 BeadChip, targeting ~2% of all CpGs in the genome. Results: Overall, co-twins showed very similar genome-wide DNA methylation profiles. Since observed differences were almost exclusively caused by variable cellular composition, an original marker-based adjustment strategy was developed to eliminate such variation at affected CpGs. Among adjusted and unchanged CpGs 3153 were differentially methylated between the heavy and light co-twins at nominal significance (p<0.01), of which 45 showed absolute mean β-value differences >0.05 (max=0.08). Deep bisulfite sequencing of eight such loci revealed that differences remained in the range of technical variation, arguing against a reproducible biological effect. Analysis of methylation in repetitive elements using methylation-dependent primer extension assays also indicated no significant intra-pair differences. Conclusions: Severe intrauterine growth differences observed within these MZ twins are not associated with long-lasting DNA methylation differences in cells composing saliva, detectable with up-to-date technologies. Additionally, our results indicate that uneven cell type composition can lead to spurious results and should be addressed in epigenomic studies. DNA methylation profiles of saliva from 17 Adult Female MZ MC Twins discordant for birth weight.