Dataset Information

Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation.

ABSTRACT:

Background

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). 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.

Results

The 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.

Conclusion

The 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.

SUBMITTER: Haque MM

PROVIDER: S-EPMC4888261 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation.

Haque M Muksitul MM Nilsson Eric E EE Holder Lawrence B LB Skinner Michael K MK

BMC genomics 20160601

<h4>Background</h4>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). The germline (e.g. sperm) transmission of epimutations is associated with epigenetic transgenerational inheritanc ...[more]

PMID: 27245821

Similar Datasets

Project description:Epigenetic inheritance is the transmission of altered gene expression states across dividing cells without DNA sequence variation. Induced epigenetic changes (epimutations) have been extensively studied, but importantly, epimutations also occur spontaneously in a manner reminiscent of DNA sequence change. Small RNAs are established as a source of spontaneous epimutations which transmit gene expression changes over multiple generations in C.elegans. These changes are generally short lived, but rarely long-lived changes occur. Given that chromatin state is a critical regulator of gene expression, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational epigenetic inheritance. We compared the chromatin profiles and gene expression profiles at matched time points from a twenty generation bottlenecked lineage of C.elegans. We found that heritable changes in gene expression arose at a higher rate than the estimate for DNA sequence variation, indicating that these were true epigenetic events. In addition to recapitulating the known role for small RNAs, we provide evidence for chromatin mediated epimutations as an alternative mechanism driving epigenetic inheritance. Chromatin epimutations were heritable, enriched in the germline and synchronised with inherited gene expression changes. As with small RNA mediated epimutations, they were generally short lived with a tendency to resolve to baseline after 2-3 generations. A subset of chromatin epimutations however were long lasting, and these were uniquely enriched in piRNA clusters. Genes with long lived epimutations were implicated in multiple components of xenobiotic response pathways. This points to a mechanism for epigenetic ‘anticipation’ of environmental stressors. Adaptive traits driven by epimutations may be selected for under adverse conditions and lost on return to normal conditions, enabling soft adaptation in the absence of genetic sequence change.

Dataset Information

Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation.

Background

Results

Conclusion

Publications

Genomic Clustering of differential DNA methylated regions (epimutations) associated with the epigenetic transgenerational inheritance of disease and phenotypic variation.

Similar Datasets

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