Abstract
BackgroundPreviously a variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated.ResultsThe epimutations from six different environmental exposures were found to be predominantly exposure specific with negligible overlap. The current report describes a major genomic feature of all the unique epimutations identified (535) as a very low (<10 CpG/100 bp) CpG density in sperm and somatic cells associated with transgenerational disease. The genomic locations of these epimutations were found to contain DMRs with small clusters of CpG within a general region of very low density CpG. The potential role of these epimutations on gene expression is suggested to be important.ConclusionsObservations suggest a potential regulatory role for lower density CpG regions termed “CpG deserts”. The potential evolutionary origins of these regions is also discussed.
Highlights
A variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm
Each individual DMR was identified with a methylated DNA immunoprecipitation (MeDIP) procedure followed by a genome wide promoter tiling array (MeDIP-Chip) protocol [13,14,15,16,17,18,19]
In addition to the existing knowledge on the role of high density Cytosines adjacent to guanine (CpG) islands and shores on the regulation of genome activity, the characterization of the transgenerational sperm and somatic epimutations suggests the importance of low density CpG regions, termed CpG deserts
Summary
A variety of environmental toxicants were found to promote the epigenetic transgenerational inheritance of disease through differential DNA methylation regions (DMRs), termed epimutations, present in sperm. The transgenerational epimutations in sperm and somatic cells identified in a number of previous studies were further investigated. Functional studies of the role of these CpG islands has lead to the dogma that they are the regulatory regions for DNA methylation. More recent marks such as 5 hydroxymethyl-cytosine [4] have expanded our understanding of the DNA methylation. CpG islands have been thought to be the primary regions to regulate gene expression [3], more recent data suggests that the lower density CpG shores of islands may be important [6]
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