The SUMO ligase Su(var)2-10 links piRNA-guided target recognition to chromatin silencing

Regulation of transcription is the main mechanism responsible for precise control of gene expression. While the majority of transcriptional regulation is mediated by a multitude of DNA-binding transcription factors that bind to regulatory gene regions, an elegant alternative strategy employs small RNA guides, piwi-interacting RNAs (piRNAs) to identify targets of transcriptional repression. Here we show that in Drosophila the small ubiquitin-like protein SUMO and the SUMO E3 ligase Su(var)2-10 are required for piRNA-guided deposition of repressive chromatin marks and transcriptional silencing of piRNA targets. Su(var)2-10 links the piRNA-guided target recognition complex to the silencing effector by binding the piRNA/Piwi complex and inducing SUMO-dependent recruitment of the SetDB1/Wde histone methyltransferase effector. We propose that in Drosophila, the nuclear piRNA pathway has co-opted a conserved mechanism of SUMO-dependent recruitment of the SetDB1/Wde chromatin modifier to confer repression of genomic parasites. Highlights- piRNA-induced transposon silencing requires SUMO and the SUMO E3 ligase Su(var)2-10 - Su(var)2-10 links the target recognition complex to the silencing effector - Su(var)2-10 binds the piRNA-guided target recognition complex and deposits SUMO on target chromatin - Su(var)2-10 induces SUMO-dependent recruitment of the SetDB1/Wde histone methyltransferase to target loci