A new model of transposon silencing and its possible effects on genome regulation.

The control of transposable elements is mediated by small non-coding RNAs deriving from transposon-rich heterochromatic regions that function as small RNA-generating loci. These clusters are transcribed and the precursor transcripts are processed to generate piRNAs and endo-siRNAs, which silence transposable elements. The flamenco locus is a Drosophila small RNA cluster that controls gypsy and other transposable elements. In this study, we provide genetic and molecular evidence that flamenco permissive alleles can induce specific developmental phenotypes triggered by gypsy-induced mutations at distant euchromatic loci, suggesting a modulation of the flamenco function by gypsy. New gypsy insertions induce a cosuppression of gypsy and of some specific flamenco sequences from which small RNAs against gypsy originate, with consequences to piRNA production both in ovary and somatic tissues. Expression of other transposable elements regulated by flamenco appear downregulated in somatic tissues, confirming the effect on the flamenco activity. This regulatory mechanism does not seem to depend on increase in the heterochromatic marks H3K9me3 and H3K27me3, suggesting a post-transcriptional regulation that involves both endo-siRNA and piRNA production. We propose that new gypsy euchromatic insertions trigger a post-transcriptional silencing of gypsy sense and antisense sequences, which modifies the flamenco activity. This mechanism interferes with the regulation of a number of biological processes probably by influencing genome regulation.