Abstract
A variety of environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. The process involves exposure of a gestating female and the developing fetus to environmental factors that promote permanent alterations in the epigenetic programming of the germline. The molecular aspects of the phenomenon involve epigenetic modifications (epimutations) in the germline (e.g. sperm) that are transmitted to subsequent generations. The current study integrates previously described experimental epigenomic transgenerational data and web-based bioinformatic analyses to identify genomic features associated with these transgenerationally transmitted epimutations. A previously identified genomic feature associated with these epimutations is a low CpG density (<12/100bp). The current observations suggest the transgenerational differential DNA methylation regions (DMR) in sperm contain unique consensus DNA sequence motifs, zinc finger motifs and G-quadruplex sequences. Interaction of molecular factors with these sequences could alter chromatin structure and accessibility of proteins with DNA methyltransferases to alter de novo DNA methylation patterns. G-quadruplex regions can promote the opening of the chromatin that may influence the action of DNA methyltransferases, or factors interacting with them, for the establishment of epigenetic marks. Zinc finger binding factors can also promote this chromatin remodeling and influence the expression of non-coding RNA. The current study identified genomic features associated with sperm epimutations that may explain in part how these sites become susceptible for transgenerational programming.
Highlights
A number of environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation [1,2,3,4,5,6]
Germline epigenetic marks are altered during early fetal development and these environmentally induced epigenetic modifications can be transmitted to subsequent generations
The initial genomic feature associated with all the epimutations previously identified was a low CpG density (,12 GpG/100bp), other genomic features are anticipated
Summary
A number of environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation [1,2,3,4,5,6]. The initiation of this transgenerational inheritance process involves exposure of a gestating female and the developing fetus during gonadal sex determination to environmental factors (e.g. toxicants). Environmentally-induced epigenetic modifications in the germline have been shown to involve DNA methylation changes that are transmitted transgenerationally [6]. These germline epigenetic modifications induce epigenetic alterations in somatic tissues which correlate with transgenerational transcriptome changes [9] and phenotypic abnormalities [10]
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