Fig. 1.

Schematic model of piRNA-guided de novo DNA methylation of transposons in mouse male germline in a time window from embryonic day 15.5 (E15.5) to postnatal day 3 (P3). MIWI2 engages in the ping–pong cycle with MILI, leading to the initiation of effector piRNA production. Loading of MIWI2 with resulting effector piRNAs induces its translocation into the nucleus. The MIWI2/piRNA complex then targets young transposon RNA through high complementarity of base-pairing, which subsequently licences the recruitment of SPOCD1 and the associated DNA methylation and chromatin remodeling machinery, resulting in targeted DNA methylation of promotor elements upstream of transposon loci