Heterochromatin formation in mammalian cells: interaction between histones and HP1 proteins

Mol Cell. 2001 Apr;7(4):729-39. doi: 10.1016/s1097-2765(01)00218-0.


Members of the heterochromatin protein 1 (HP1) family are silencing nonhistone proteins. Here, we show that in P19 embryonal carcinoma (EC) nuclei, HP1 alpha, beta, and gamma form homo- and heteromers associated with nucleosomal core histones. In vitro, all three HP1s bind to tailed and tailless nucleosomes and specifically interact with the histone-fold of histone H3. Furthermore, HP1alpha interacts with the linker histone H1. HP1alpha binds to H3 and H1 through its chromodomain (CD) and hinge region, respectively. Interestingly, the Polycomb (Pc1/M33) CD also interacts with H3, and HP1alpha and Pc1/M33 binding to H3 is severely impaired by CD mutations known to abrogate HP1 and Polycomb silencing in Drosophila. These results define a novel function for the conserved CD and suggest that HP1 self-association and histone binding may play a crucial role in HP1-mediated heterochromatin assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / physiology
  • Chromosomal Proteins, Non-Histone / chemistry
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Conserved Sequence
  • Drosophila
  • Embryonal Carcinoma Stem Cells
  • Epitopes / genetics
  • Heterochromatin / genetics
  • Heterochromatin / metabolism*
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • In Vitro Techniques
  • Mammals
  • Mice
  • Molecular Sequence Data
  • Mutagenesis / physiology
  • Neoplastic Stem Cells
  • Nucleosomes / genetics
  • Nucleosomes / metabolism
  • Oligopeptides
  • Peptides / genetics
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • Protein Structure, Tertiary
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism


  • Cbx2 protein, mouse
  • Chromosomal Proteins, Non-Histone
  • Epitopes
  • Heterochromatin
  • Histones
  • Nucleosomes
  • Oligopeptides
  • Peptides
  • Polycomb-Group Proteins
  • Repressor Proteins
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • FLAG peptide
  • Polycomb Repressive Complex 1