Figure 1.

Proposed mechanism for piRNA-induced DNA methylation in male germ cells. Primary piRNAs produced from TE-rich piRNA clusters join Piwi (Mili and/or Miwi2) proteins. Sense (blue) and antisense (red) piRNAs are amplified in the ping-pong cycle. Piwi–piRNAs complexes recognize nascent TE transcripts in the nucleus and recruit chromatin modifiers to TE genomic loci. Subsequent changes in histone marks (H3K4 methylation loss, H3K9 methylation gain, green diamonds) induce the de novo activity of the Dnmt3A–Dnmt3L tetrameric complex to establish methylation patterns.