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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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Visualization of DNA motifs associated with epigenetic transgenerational inheritance in selected sets of sequences: (A) incidence of EDM1 and EDM2 in a set of confirmed DMR from vinclozolin-lineage and (B) incidence of EDM1 and EDM2 in a set of confirmed DMR from lineage originated from a variety of exposures listed.The colored legend for EDM1 versus EDM2 motifs are presented.
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pone-0100194-g008: Visualization of DNA motifs associated with epigenetic transgenerational inheritance in selected sets of sequences: (A) incidence of EDM1 and EDM2 in a set of confirmed DMR from vinclozolin-lineage and (B) incidence of EDM1 and EDM2 in a set of confirmed DMR from lineage originated from a variety of exposures listed.The colored legend for EDM1 versus EDM2 motifs are presented.

Mentions: Schematic visualization of the features analyzed in selected sets of transgenerational DMRs previously confirmed for the vinclozolin and other exposure DMR groups are shown in Figure 8A,B. The locations of EDM1 and EDM2 in selected sequences are shown in Figure 8. Detailed schematic representations of the locations of these features in selected DMR from the vinclozolin lineage exposure are shown in Figure 9. Therefore, a number of genomic features were identified and appeared to be associated with the transgenerational sperm epimutations investigated.


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

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

Visualization of DNA motifs associated with epigenetic transgenerational inheritance in selected sets of sequences: (A) incidence of EDM1 and EDM2 in a set of confirmed DMR from vinclozolin-lineage and (B) incidence of EDM1 and EDM2 in a set of confirmed DMR from lineage originated from a variety of exposures listed.The colored legend for EDM1 versus EDM2 motifs are presented.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0100194-g008: Visualization of DNA motifs associated with epigenetic transgenerational inheritance in selected sets of sequences: (A) incidence of EDM1 and EDM2 in a set of confirmed DMR from vinclozolin-lineage and (B) incidence of EDM1 and EDM2 in a set of confirmed DMR from lineage originated from a variety of exposures listed.The colored legend for EDM1 versus EDM2 motifs are presented.
Mentions: Schematic visualization of the features analyzed in selected sets of transgenerational DMRs previously confirmed for the vinclozolin and other exposure DMR groups are shown in Figure 8A,B. The locations of EDM1 and EDM2 in selected sequences are shown in Figure 8. Detailed schematic representations of the locations of these features in selected DMR from the vinclozolin lineage exposure are shown in Figure 9. Therefore, a number of genomic features were identified and appeared to be associated with the transgenerational sperm epimutations investigated.

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