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SRNA drives epigenetic changes in F1 hybrids

ABSTRACT: Hybrid Arabidopsis plants undergo epigenetic reprogramming producing decreased levels of 24nt siRNAs and altered patterns of DNA methylation that can affect gene expression. Driving the changes in methylation are the processes Trans Chromosomal Methylation (TCM) and Trans Chromosomal deMethylation (TCdM). In TCM/TCdM the methylation state of one allele is altered to resemble the other allele. These changes in DNA methylation and the associated changes in small RNA levels in the F1 hybrid can be maintained in subsequent generations and affect hundreds of regions in the F2 epigenome. The inheritance of these altered epigenetic states varies in F2 individuals resulting in individuals with genetically identical loci displaying different epigenetic states and gene expression profiles. At these regions the change in methylation is associated with the presence of small RNAs. Loci without any sRNA activity can have altered methylation states, suggesting that a sRNA-independent mechanism may also contribute to the altered methylation state of the F1 and F2 generations.

ORGANISM(S): Arabidopsis thaliana

PROVIDER: GSE85551 | GEO | 2016/08/30

SECONDARY ACCESSION(S): PRJNA338792

REPOSITORIES: GEO

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Project description:Background: DNA methylation (DNAme) erasure and reacquisition occurs during prenatal male germ cell development; some further remodelling takes place after birth during spermatogenesis. Environmental insults during germline epigenetic reprogramming may affect DNAme, presenting a potential mechanism for transmission of environmental exposures across multiple generations. Objectives: We investigated how germ cell DNAme is impacted by lifetime exposures to diets containing either low or high, clinically relevant, levels of the methyl donor folic acid and whether resulting DNAme alterations were inherited in germ cells of male offspring of subsequent generations. Materials and Methods: Female mice were placed on a 7-fold folic acid deficient (7FD) and 10- or 20-fold supplemented (10FS and 20FS) diets before and during pregnancy. Resulting F1 litters were weaned on the respective diets. F2 and F3 males received control diets. Genome-wide DNAme was assessed in F1 spermatogonia, and in F1, F2 and F3 sperm. Results: In F1 germ cells, a greater number of differentially methylated cytosines (DMCs) was observed in spermatogonia as compared with F1 sperm for all folic acid diets. DMCs were lower in number in F2 versus F1 sperm, while an unexpected increase was found in F3 sperm. DMCs were predominantly hypomethylated, with genes in neurodevelopmental pathways commonly affected in F1, F2 and F3 male germ cells. While no DMCs were found to be inherited inter- or transgenerationally, we observed over-representation of repetitive elements, particularly young LINEs. Discussion and Conclusion: These results suggest that the prenatal window is the time most susceptible to folate-induced alterations in sperm DNAme in male germ cells. Altered methylation of specific sites in F1 sperm was not present in later generations. However, the finding of hypomethylated young LINE1 elements in sperm from F1 to F3 males provides insight into potential mechanisms of epigenetic inheritance of the effects of folate deficiency and supplementation.

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SRNA drives epigenetic changes in F1 hybrids

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