Abstract
BackgroundDNA methylation is the most studied form of epigenetic regulation, a process by which chromatin composition and transcription factor binding is altered to influence tissue specific gene expression and differentiation. Such tissue specific methylation patterns are investigated as biomarkers for cancer and cell-free fetal DNA using various methodologies.ResultsWe have utilized methylation DNA immunoprecipitation (MeDIP) and real-time quantitative PCR to investigate the inter-individual methylation variability of differentially methylated regions (DMRs) on chromosomes 18 and 21. We have characterized 15 newly selected and seven previously validated DMRs in 50, 1st trimester Chorionic villus samplings (CVS) and 50 female non-pregnant peripheral blood (WBF) samples. qPCR results from MeDIP and genomic DNA (Input) assays were used to calculate fold enrichment values for each DMR. For all regions tested, enrichment was higher in CVS than in WBF samples with mean enrichments ranging from 0.22 to 6.4 and 0.017 to 1 respectively. Despite inter-individual variability, mean enrichment values for CVS were significantly different than those for WBF in all DMRs tested (p < 0.01). This observation is reinforced by the absence of overlap in CVS and WBF enrichment value distributions for 15 of 22 DMRs.ConclusionsOur work provides an expansion in the biomarker panel available for non-invasive prenatal diagnosis (NIPD) using the MeDIP-qPCR methology for Down syndrome and can eventually provide the starting point towards the development for assays towards the detection of Edwards syndrome. Furthermore, our data indicate that inter-experimental and inter-individual variation in methylation is apparent, yet the difference in methylation status across tissues is large enough to allow for robust tissue specific methylation identification.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-014-0073-8) contains supplementary material, which is available to authorized users.
Highlights
DNA methylation is the most studied form of epigenetic regulation, a process by which chromatin composition and transcription factor binding is altered to influence tissue specific gene expression and differentiation
Using the above criteria we identified a set of 40 candidate differentially methylated regions (DMRs) between Chorionic villus samplings (CVS) and WBF from the microarray data [12]
This set was subsequently screened in a cohort of six CVS and six WBF to calculate the enrichment values for each DMR (Additional file 1)
Summary
DNA methylation is the most studied form of epigenetic regulation, a process by which chromatin composition and transcription factor binding is altered to influence tissue specific gene expression and differentiation. In vertebrates DNA methylation is a conserved epigenetic modification by which DNA methyltransferases add a methyl group to carbon 5 of cytosine residues present in CpG dinucleotides This modification is the most studied form of epigenetic regulation and has been strongly associated with chromosomal stability and imprinting control [1]. DNA methylation occurs primarily in CpG islands (GGIs) and shores both in coding and non-coding regions of the genome, with gene regulatory regions such as promoters and first exons being a frequent methylation target [4] Due to this integral relationship with gene expression regulation, DNA methylation patterns are very closely associated with developmental processes and differentiation. These tissue specific differentially methylated regions (tDMRs) are currently under investigation for their utility as biomarkers for disease progression and prognosis, in the field of cancer research, disease detection and response to treatment [7]
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