Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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DNA methylation alterations in response to pesticide exposure in vitro

ABSTRACT: Genome wide DNA methylation profiling of DNA from K562 cells treated with three commonly used pesticides and control (EtOH). The Illumina Infinium 27k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 27,000 CpGs in DNA samples. Bisulphite converted DNA from the samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip. 7 pesticides were used.

ORGANISM(S): Homo sapiens

SUBMITTER: xiao zhang

PROVIDER: E-GEOD-38646 | 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.

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DNA methylation alterations in response to pesticide exposure in vitro

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