Abstract
BackgroundA variety of environmental factors have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation in numerous species. Exposure to environmental factors such as toxicants can promote epigenetic changes (epimutations) involving alterations in DNA methylation to produce specific differential DNA methylation regions (DMRs). The germline (e.g. sperm) transmission of epimutations is associated with epigenetic transgenerational inheritance phenomena. The current study was designed to determine the genomic locations of environmentally induced transgenerational DMRs and assess their potential clustering.ResultsThe exposure specific DMRs (epimutations) from a number of different studies were used. The clustering approach identified areas of the genome that have statistically significant over represented numbers of epimutations. The location of DMR clusters was compared to the gene clusters of differentially expressed genes found in tissues and cells associated with the transgenerational inheritance of disease. Such gene clusters, termed epigenetic control regions (ECRs), have been previously suggested to regulate gene expression in regions spanning up to 2-5 million bases. DMR clusters were often found to associate with inherent gene clusters within the genome.ConclusionThe current study used a number of epigenetic datasets from previous studies to identify novel DMR clusters across the genome. Observations suggest these clustered DMR within an ECR may be susceptible to epigenetic reprogramming and dramatically influence genome activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2748-5) contains supplementary material, which is available to authorized users.
Highlights
A variety of environmental factors have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation in numerous species
The current study extends these previous studies that used transgenerational transcriptome cluster analysis to investigate the clustering of the associated sperm DNA methylation regions (DMRs) epimutations (i.e. DMR clusters) and relationships with differential gene expression clusters
The current study demonstrates that environmentally induced epigenetic transgenerational inheritance of F3 generation sperm DMRs often cluster on the genome and associate with the previously identified gene clusters within epigenetic control regions (ECR)
Summary
A variety of environmental factors have been shown to promote the epigenetic transgenerational inheritance of disease and phenotypic variation in numerous species. Exposure to environmental factors such as toxicants can promote epigenetic changes (epimutations) involving alterations in DNA methylation to produce specific differential DNA methylation regions (DMRs). An increasing number of studies in a wide variety of species have demonstrated that altered epigenetic information (such as DNA methylation, histone modifications, long non-coding RNA) can be passed on from one generation to the through the germline (sperm and eggs) [1]. Environmental exposures such as nutrition, stress and toxicants can lead to germline epigenome changes (epimutations) that promote disease and. The epigenome has certain regions which exhibit groupings of epigenetic features or associated genomic components [9, 10]
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