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Identification of genomic features in environmentally induced epigenetic transgenerational inherited sperm epimutations.

Guerrero-Bosagna C, Weeks S, Skinner MK - PLoS ONE (2014)

Bottom Line: A previously identified genomic feature associated with these epimutations is a low CpG density (<12/100bp).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America; Department of Physics, Biology and Chemistry, Linköping University, Linköping, Sweden.

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.

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Related in: MedlinePlus

Density of incidences of (A) EDM1 and (B) EDM2 in sets of transgenerational DMR.The vinclozolin DMR, combination of plastics (BIP), pesticide (PIP), jet fuel (JIP) and dioxin (HIP) DMR, and a random set of genomic sites were investigated. The number of EDM1 or EDM2 sites per DMR is presented with the mean± SEM.
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pone-0100194-g005: Density of incidences of (A) EDM1 and (B) EDM2 in sets of transgenerational DMR.The vinclozolin DMR, combination of plastics (BIP), pesticide (PIP), jet fuel (JIP) and dioxin (HIP) DMR, and a random set of genomic sites were investigated. The number of EDM1 or EDM2 sites per DMR is presented with the mean± SEM.

Mentions: The possibility that an altered density of EDM1 or EDM2 motifs could be observed in DMR sets versus the random set was examined. No significant changes were observed for the density of EDM1 or EDM2 in DMR from the exposure groups in reference to the random set (Figure 5). Given the composition of EDM1 in terms of being an A/T rich sequence and the reported role of A/T rich sequences as a recognition site for de novo DNA methylation [47], the density distribution of this feature across the different sets of DMR was also analyzed. Differences in the density distribution of A/T strings were found between the plastics, pesticides, dioxin and jet fuel groups and equivalent random sets of sequences. There is an overall reduction in the density of A/T strings in DMRs from these groups in comparison to the random set (Figure 6 A–E; p<0.01). However, A/T string density in the vinclozolin group is similar to the random distribution (Figure 6F).


Identification of genomic features in environmentally induced epigenetic transgenerational inherited sperm epimutations.

Guerrero-Bosagna C, Weeks S, Skinner MK - PLoS ONE (2014)

Density of incidences of (A) EDM1 and (B) EDM2 in sets of transgenerational DMR.The vinclozolin DMR, combination of plastics (BIP), pesticide (PIP), jet fuel (JIP) and dioxin (HIP) DMR, and a random set of genomic sites were investigated. The number of EDM1 or EDM2 sites per DMR is presented with the mean± SEM.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4061094&req=5

pone-0100194-g005: Density of incidences of (A) EDM1 and (B) EDM2 in sets of transgenerational DMR.The vinclozolin DMR, combination of plastics (BIP), pesticide (PIP), jet fuel (JIP) and dioxin (HIP) DMR, and a random set of genomic sites were investigated. The number of EDM1 or EDM2 sites per DMR is presented with the mean± SEM.
Mentions: The possibility that an altered density of EDM1 or EDM2 motifs could be observed in DMR sets versus the random set was examined. No significant changes were observed for the density of EDM1 or EDM2 in DMR from the exposure groups in reference to the random set (Figure 5). Given the composition of EDM1 in terms of being an A/T rich sequence and the reported role of A/T rich sequences as a recognition site for de novo DNA methylation [47], the density distribution of this feature across the different sets of DMR was also analyzed. Differences in the density distribution of A/T strings were found between the plastics, pesticides, dioxin and jet fuel groups and equivalent random sets of sequences. There is an overall reduction in the density of A/T strings in DMRs from these groups in comparison to the random set (Figure 6 A–E; p<0.01). However, A/T string density in the vinclozolin group is similar to the random distribution (Figure 6F).

Bottom Line: A previously identified genomic feature associated with these epimutations is a low CpG density (<12/100bp).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.

View Article: PubMed Central - PubMed

Affiliation: Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America; Department of Physics, Biology and Chemistry, Linköping University, Linköping, Sweden.

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.

Show MeSH
Related in: MedlinePlus