Identification of SUMO-dependent chromatin-associated transcriptional repression components by a genome-wide RNAi screen

Mol Cell. 2008 Mar 28;29(6):742-54. doi: 10.1016/j.molcel.2007.12.032.


SUMO modification of many transcription factors is linked to transcriptional repression. The molecular mechanisms by which SUMO attachment represses transcription are largely unknown. Here we report a genome-wide RNA interference screen in Drosophila melanogaster cells for components regulating and mediating SUMO-dependent transcriptional repression. Analysis of >21,000 double-stranded RNAs (dsRNAs) identified 120 genes whose dsRNA-mediated knockdowns impaired SUMO-dependent transcriptional repression. Several of these genes encode chromatin-associated proteins, including the ATP-dependent chromatin remodeler Mi-2, the D. melanogaster ortholog of the C. elegans protein MEP-1, and the polycomb protein Sfmbt. Knockdown of these proteins did not impair SUMO conjugation, demonstrating that they act downstream of SUMO attachment. Biochemical analyses revealed that MEP-1, Mi-2, and Sfmbt interact with each other, bind to SUMO, and are recruited to promoters in a SUMOylation-dependent manner. Our results suggest that MEP-1, Mi-2, and Sfmbt are part of a common repression complex established by DNA-bound SUMO-modified transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatin / genetics*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Gene Expression Regulation
  • Genome
  • Histone Deacetylases / genetics
  • Histone Deacetylases / metabolism
  • Mammals
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex
  • Promoter Regions, Genetic
  • RNA Interference*
  • RNA, Double-Stranded / genetics
  • SUMO-1 Protein / metabolism*
  • Species Specificity
  • Transcription, Genetic*


  • Chromatin
  • Drosophila Proteins
  • RNA, Double-Stranded
  • SUMO-1 Protein
  • Histone Deacetylases
  • Mi-2 Nucleosome Remodeling and Deacetylase Complex