Su(var)2-10 and the SUMO Pathway Link piRNA-Guided Target Recognition to Chromatin Silencing

Mol Cell. 2020 Feb 6;77(3):556-570.e6. doi: 10.1016/j.molcel.2019.11.012. Epub 2019 Dec 31.


Regulation of transcription is the main mechanism responsible for precise control of gene expression. Whereas the majority of transcriptional regulation is mediated by 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.

Keywords: SUMO; Su(var)2-10; chromatin; heterochromatin; piRNA; silencing; transposon.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism
  • Cell Nucleus / metabolism
  • Chromatin / genetics
  • Chromatin / metabolism
  • DNA Transposable Elements
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Gene Expression Regulation / genetics
  • Gene Silencing / physiology
  • Protein Binding
  • Protein Inhibitors of Activated STAT / genetics
  • Protein Inhibitors of Activated STAT / metabolism*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • Small Ubiquitin-Related Modifier Proteins / genetics
  • Small Ubiquitin-Related Modifier Proteins / metabolism*
  • Transcription, Genetic / genetics


  • Argonaute Proteins
  • Chromatin
  • DNA Transposable Elements
  • Drosophila Proteins
  • Protein Inhibitors of Activated STAT
  • RNA, Small Interfering
  • Small Ubiquitin-Related Modifier Proteins
  • Su(var)2-10 protein, Drosophila