Heterochromatin protein 1 forms distinct complexes to direct histone deacetylation and DNA methylation

Nat Struct Mol Biol. 2012 Apr 15;19(5):471-7, S1. doi: 10.1038/nsmb.2274.


DNA methylation, methylation of histone H3 at Lys9 (H3K9me3) and hypoacetylated histones are common molecular features of heterochromatin. Important details of their functions and inter-relationships remain unclear, however. In Neurospora crassa, H3K9me3 directs DNA methylation through a complex containing heterochromatin protein 1 (HP1) and the DNA methyltransferase DIM-2. We identified a distinct HP1 complex, HP1, CDP-2, HDA-1 and CHAP (HCHC), and found that it is responsible for silencing independently of DNA methylation. HCHC defects cause hyperacetylation of centromeric histones, greater accessibility of DIM-2 and hypermethylation of centromeric DNA. Loss of HCHC also causes mislocalization of the DIM-5 H3K9 methyltransferase at a subset of interstitial methylated regions, leading to selective DNA hypomethylation. We demonstrate that HP1 forms distinct DNA methylation and histone deacetylation complexes that work in parallel to assemble silent chromatin in N. crassa.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Methylation*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • Gene Silencing*
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Histones / genetics
  • Histones / metabolism*
  • Methyltransferases / genetics
  • Methyltransferases / metabolism
  • Mutation
  • Neurospora crassa / genetics
  • Neurospora crassa / metabolism*


  • Chromosomal Proteins, Non-Histone
  • DNA, Fungal
  • Fungal Proteins
  • Heterochromatin
  • Histones
  • heterochromatin-specific nonhistone chromosomal protein HP-1
  • Methyltransferases