Abstract: Chromatin marks were proposed to be able to mediate epigenetic inheritance – transmission of the information that is not encoded in DNA sequence – in cell lineages. On the other hand, transmission of epigenetic information from one generation to the next was demonstrated in only few cases and underlying molecular mechanisms remained poorly understood. 

We showed that in Drosophila specific class of small non-coding RNA, piRNA, provide trans-generational epigenetic memory that is independent of chromatin marks and in fact act upstream of chromatin changes. piRNA serve as guides for repression of diverse transposable elements in germ cells of Metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs.

Trans-generationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation. Inherited piRNAs induce installment of the H3K9me3 mark on genomic piRNA cluster sequences followed by recruitment of protein complex necessary for piRNA biogenesis.