Heterochromatin protein 1α interacts with parallel RNA and DNA G-quadruplexes

Nucleic Acids Res. 2020 Jan 24;48(2):682-693. doi: 10.1093/nar/gkz1138.


The eukaryotic genome is functionally organized into domains of transcriptionally active euchromatin and domains of highly compact transcriptionally silent heterochromatin. Heterochromatin is constitutively assembled at repetitive elements that include the telomeres and centromeres. The histone code model proposes that HP1α forms and maintains these domains of heterochromatin through the interaction of its chromodomain with trimethylated lysine 9 of histone 3, although this interaction is not the sole determinant. We show here that the unstructured hinge domain, necessary for the targeting of HP1α to constitutive heterochromatin, recognizes parallel G-quadruplex (G4) assemblies formed by the TElomeric Repeat-containing RNA (TERRA) transcribed from the telomere. This provides a mechanism by which TERRA can lead to the enrichment of HP1α at telomeres to maintain heterochromatin. Furthermore, we show that HP1α binds with a faster association rate to DNA G4s of parallel topology compared to antiparallel G4s that bind slowly or not at all. Such G4-DNAs are found in the regulatory regions of several oncogenes. This implicates specific non-canonical nucleic acid structures as determinants of HP1α function and thus RNA and DNA G4s need to be considered as contributors to chromatin domain organization and the epigenome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Centromere / genetics
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA / genetics*
  • DNA-Binding Proteins / genetics*
  • Euchromatin / genetics
  • G-Quadruplexes*
  • Heterochromatin / genetics
  • Histones
  • Humans
  • Mice
  • NIH 3T3 Cells
  • RNA / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Telomere / genetics
  • Transcription Factors / genetics*


  • CBX5 protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Dmrt2 protein, mouse
  • Euchromatin
  • Heterochromatin
  • Histones
  • Transcription Factors
  • Chromobox Protein Homolog 5
  • RNA
  • DNA