Epigenetic reprogramming of embryonic mouse germ cells involves DNA demethylation of the genome that is accompanied by derepression of transposable elements (TEs). Threatening the genome's integrity, TE activation is efficiently countered by the concerted action of de novo DNA methylation and PIWI-interacting small RNAs (piRNAs). Recent studies have closely examined the subcellular localization of various piRNA pathway proteins in fetal prospermatogonia of wild-type and piRNA pathway mutant mice. Our survey highlights hierarchies and partnerships between the members of this ancient defensive mechanism. Overall, the elaborate cytoplasmic compartmentalization of the piRNA pathway in fetal prospermatogonia provides a highly informative context to aid our understanding of the mouse piRNA pathway.
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