Role of CpG deserts in the epigenetic transgenerational inheritance of differential DNA methylation regions

Background: Previously 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. Results: The 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. Conclusions: Observations suggest a potential regulatory role for lower density CpG regions termed CpG deserts. The potential evolutionary origins of these regions is also discussed.