Pericentric heterochromatin generated by HP1 protein interaction-defective histone methyltransferase Suv39h1

J Biol Chem. 2013 Aug 30;288(35):25285-25296. doi: 10.1074/jbc.M113.470724. Epub 2013 Jul 7.

Abstract

Pericentric regions form epigenetically organized silent heterochromatin structures that accumulate histone H3 lysine 9 trimethylation (H3K9me3) and HP1. At pericentric regions, Suv39h is the major enzyme that generates H3K9me3. Suv39h also interacts directly with HP1, a methylated H3K9-binding protein. However, it is not well characterized how HP1 interaction is important for Suv39h accumulation and Suv39h-mediated H3K9me3 formation at the pericentromere. To address this, we introduced the HP1 binding-defective N-terminally truncated mouse Suv39h1 (ΔN) into Suv39h-deficient embryonic stem cells. Interestingly, pericentric accumulation of ΔN and ΔN-mediated H3K9me3 was observed to recover, but HP1 accumulation was only marginally restored. ΔN also rescued DNA methyltransferase Dnmt3a and -3b accumulation and DNA methylation of the pericentromere. In contrast, other pericentric heterochromatin features, such as ATRX protein association and H4K20me3, were not recovered. Finally, derepressed major satellite repeats were partially silenced by ΔN expression. These findings clearly showed that the Suv39h-HP1 binding is dispensable for pericentric H3K9me3 and DNA methylation, but this interaction and HP1 recruitment/accumulation seem to be crucial for complete formation of heterochromatin.

Keywords: ATRX; Chromatin Structure; DNA Methylation; Dnmt3; HP1; Heterochromatin; Histone Methylation; Mammal; Suv39h.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Animals
  • Chromobox Protein Homolog 5
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA (Cytosine-5-)-Methyltransferases / genetics
  • DNA (Cytosine-5-)-Methyltransferases / metabolism
  • DNA Helicases / genetics
  • DNA Helicases / metabolism
  • DNA Methylation / physiology*
  • DNA Methyltransferase 3A
  • DNA Methyltransferase 3B
  • Embryonic Stem Cells
  • HEK293 Cells
  • Heterochromatin / genetics
  • Heterochromatin / metabolism*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • X-linked Nuclear Protein

Substances

  • Chromosomal Proteins, Non-Histone
  • DNMT3A protein, human
  • Dnmt3a protein, mouse
  • Heterochromatin
  • Histones
  • Nuclear Proteins
  • Repressor Proteins
  • Chromobox Protein Homolog 5
  • Suv39h1 protein, mouse
  • Methyltransferases
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A
  • Histone-Lysine N-Methyltransferase
  • DNA Helicases
  • Atrx protein, mouse
  • X-linked Nuclear Protein