Metastabile Epiallele beim Menschen und ihr Einfluss auf die Suszeptibilität für Erkrankungen
Entwicklungsbiologie
Reproduktionsmedizin, Urologie
Zusammenfassung der Projektergebnisse
Metastable epialleles (MEs) are genomic regions that are variably expressed due to a variation in epigenetic regulation between individuals. DNA methylation at MEs is either established stochastically prior to gastrulation or inherited through the germline. This mechanism leads to inter-individual epigenetic variation that occurs systemically across all somatic tissues. DNA methylation changes at MEs can influence the phenotype as evident in the agouti viable yellow (Avy) mouse. DNA methylation at the Avy locus controls the expression of the agouti gene, with consequences for both fur color and hyperphagic obesity. The project aimed to measure the methylation of human MEs via targeted bisulfite sequencing across sperm and blood collected from the same individual. The project focused on studying samples collected as part of the AMIGOS study. This will permit to identify whether DNA methylation variation at MEs is conserved in sperm and whether methylation at MEs escape the epigenetic reprogramming that occurs during primordial germ cell (PGC) development. Genomic regions which escape reprogramming in PGCs can leave epigenetic marks that can be possibly transmitted to the next generation. The Agilent SureSelectXT Human Methyl-Seq custom panel was designed for targeted bisulfite sequencing since it enables methylation measurement at single base resolution. This approach helps identify sequence variants that might have an influence on DNA methylation patterns. Bisulfite genomic sequencing is regarded as a gold-standard technology for DNA methylation analysis. Altogether, the hypothesis states that DNA methylation tags at certain MEs are stably inherited and could play a role in transgenerational epigenetic inheritance.
