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Significance Whether acquired epigenetic changes can escape the genome-wide epigenetic erasure in the primordial germ cells, which are the embryonic precursors of all types of germline cells and gametes, resulting in transgenerational transfer has been under debate. We have shown that an in vitro cell culture model of mouse primordial germ cells effectively recapitulates the process of germline epigenetic erasure, including DNA demethylation at both physiologically methylated and abnormally hypermethylated imprinting control regions. We also have identified examples of genomic repetitive sequences characterized by significant resistance to the genome-wide DNA demethylation process in mouse primordial germ cells and their cell culture models. Our study paves the way for mechanistic studies of transgenerational epigenetic inheritance using a cell culture model.

Erasure of DNA methylation, genomic imprints, and epimutations in a primordial germ-cell model derived from mouse pluripotent stem cells