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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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Distribution of G quadruplexes (GGGG) incidence across the transgenerational DMR sets.The percent of DMR with G-quadruplexes of sequences for all DMR (A), plastics (B), pesticides (C), dioxin (D), jet fuel (E), and vinclozolin (F) are presented compared to the random sequence data set.
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pone-0100194-g007: Distribution of G quadruplexes (GGGG) incidence across the transgenerational DMR sets.The percent of DMR with G-quadruplexes of sequences for all DMR (A), plastics (B), pesticides (C), dioxin (D), jet fuel (E), and vinclozolin (F) are presented compared to the random sequence data set.

Mentions: EDM2 was observed to be a G/C rich sequence. Interestingly, previous reports show that G quadruplexes associate with zinc finger binding sites [48] and have a role in restricting DNA methylation [49] to influence chromatin dependent epigenetic instability [50]. Therefore, the distribution of G-quadruplexes across the different sets of DMR was analyzed. Interesting differences were also found in the distribution of G-quadruplexes in the exposure lineage DMR sets versus the random set of sequences. In the plastics, pesticides, jet fuel and dioxin groups an overall increase in G-quadruplex density regarding the random group was observed (Figure 7 A–E; p<0.01). The vinclozolin group had a distribution comparable with the random set (Figure 7F).


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

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

Distribution of G quadruplexes (GGGG) incidence across the transgenerational DMR sets.The percent of DMR with G-quadruplexes of sequences for all DMR (A), plastics (B), pesticides (C), dioxin (D), jet fuel (E), and vinclozolin (F) are presented compared to the random sequence data set.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0100194-g007: Distribution of G quadruplexes (GGGG) incidence across the transgenerational DMR sets.The percent of DMR with G-quadruplexes of sequences for all DMR (A), plastics (B), pesticides (C), dioxin (D), jet fuel (E), and vinclozolin (F) are presented compared to the random sequence data set.
Mentions: EDM2 was observed to be a G/C rich sequence. Interestingly, previous reports show that G quadruplexes associate with zinc finger binding sites [48] and have a role in restricting DNA methylation [49] to influence chromatin dependent epigenetic instability [50]. Therefore, the distribution of G-quadruplexes across the different sets of DMR was analyzed. Interesting differences were also found in the distribution of G-quadruplexes in the exposure lineage DMR sets versus the random set of sequences. In the plastics, pesticides, jet fuel and dioxin groups an overall increase in G-quadruplex density regarding the random group was observed (Figure 7 A–E; p<0.01). The vinclozolin group had a distribution comparable with the random set (Figure 7F).

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