Combgap contributes to recruitment of Polycomb group proteins in Drosophila

Proc Natl Acad Sci U S A. 2016 Apr 5;113(14):3826-31. doi: 10.1073/pnas.1520926113. Epub 2016 Mar 21.


Polycomb group (PcG) proteins are responsible for maintaining the silenced transcriptional state of many developmentally regulated genes. PcG proteins are organized into multiprotein complexes that are recruited to DNA via cis-acting elements known as "Polycomb response elements" (PREs). In Drosophila, PREs consist of binding sites for many different DNA-binding proteins, some known and others unknown. Identification of these DNA-binding proteins is crucial to understanding the mechanism of PcG recruitment to PREs. We report here the identification of Combgap (Cg), a sequence-specific DNA-binding protein that is involved in recruitment of PcG proteins. Cg can bind directly to PREs via GTGT motifs and colocalizes with the PcG proteins Pleiohomeotic (Pho) and Polyhomeotic (Ph) at the majority of PREs in the genome. In addition, Cg colocalizes with Ph at a number of targets independent of Pho. Loss of Cg leads to decreased recruitment of Ph at only a subset of sites; some of these sites are binding sites for other Polycomb repressive complex 1 (PRC1) components, others are not. Our data suggest that Cg can recruit Ph in the absence of PRC1 and illustrate the diversity and redundancy of PcG protein recruitment mechanisms.

Keywords: Combgap; PREs; PcG recruitment; Polycomb; gene expression.

Publication types

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

MeSH terms

  • Animals
  • Binding Sites
  • Cell Differentiation
  • DNA / genetics
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Gene Expression Regulation, Developmental / genetics*
  • Nucleotide Motifs / genetics
  • Polycomb Repressive Complex 1 / genetics*
  • Polycomb-Group Proteins / genetics*
  • Polycomb-Group Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Pc protein, Drosophila
  • Polycomb-Group Proteins
  • Transcription Factors
  • cg protein, Drosophila
  • ph-d protein, Drosophila
  • pho protein, Drosophila
  • DNA
  • Polycomb Repressive Complex 1