Targeting of Polycomb Repressive Complex 2 to RNA by Short Repeats of Consecutive Guanines

Mol Cell. 2017 Mar 16;65(6):1056-1067.e5. doi: 10.1016/j.molcel.2017.02.003.


Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that trimethylates H3K27, a mark of repressed chromatin. Mammalian PRC2 binds RNA promiscuously, with thousands of target transcripts in vivo. But what does PRC2 recognize in these RNAs? Here we show that purified human PRC2 recognizes G > C,U ≫ A in single-stranded RNA and has a high affinity for folded guanine quadruplex (G4) structures but little binding to duplex RNAs. Importantly, G-tract motifs are significantly enriched among PRC2-binding transcripts in vivo. DNA sequences coding for PRC2-binding RNA motifs are enriched at PRC2-binding sites on chromatin and H3K27me3-modified nucleosomes. Collectively, the abundance of PRC2-binding RNA motifs rationalizes the promiscuous RNA binding of PRC2, and their enrichment at Polycomb target genes provides a means for RNA-mediated regulation.

Keywords: G-quadruplex; PRC2; Polycomb repressive complex 2; RNA binding specificity; motif; promiscuous RNA binding.

MeSH terms

  • Binding Sites
  • Chromatin / chemistry
  • Chromatin / enzymology*
  • Chromatin / genetics
  • Enhancer of Zeste Homolog 2 Protein / genetics
  • Enhancer of Zeste Homolog 2 Protein / metabolism
  • Gene Expression Regulation
  • Guanine / metabolism*
  • HEK293 Cells
  • Humans
  • Nucleic Acid Conformation
  • Nucleosomes / chemistry
  • Nucleosomes / enzymology*
  • Nucleosomes / genetics
  • Nucleotide Motifs
  • Polycomb Repressive Complex 2 / genetics
  • Polycomb Repressive Complex 2 / metabolism*
  • Protein Binding
  • RNA / chemistry
  • RNA / genetics
  • RNA / metabolism*
  • Structure-Activity Relationship
  • Transfection


  • Chromatin
  • Nucleosomes
  • Guanine
  • RNA
  • EZH2 protein, human
  • Enhancer of Zeste Homolog 2 Protein
  • Polycomb Repressive Complex 2