Selective interactions between vertebrate polycomb homologs and the SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 methylation contributes to chromosomal targeting of Polycomb group proteins

Mol Cell Biol. 2002 Aug;22(15):5539-53. doi: 10.1128/MCB.22.15.5539-5553.2002.

Abstract

Polycomb group (PcG) proteins form multimeric chromatin-associated protein complexes that are involved in heritable repression of gene activity. Two distinct human PcG complexes have been characterized. The EED/EZH2 PcG complex utilizes histone deacetylation to repress gene activity. The HPC/HPH PcG complex contains the HPH, RING1, BMI1, and HPC proteins. Here we show that vertebrate Polycomb homologs HPC2 and XPc2, but not M33/MPc1, interact with the histone lysine methyltransferase (HMTase) SUV39H1 both in vitro and in vivo. We further find that overexpression of SUV39H1 induces selective nuclear relocalization of HPC/HPH PcG proteins but not of the EED/EZH2 PcG proteins. This SUV39H1-dependent relocalization concentrates the HPC/HPH PcG proteins to the large pericentromeric heterochromatin domains (1q12) on human chromosome 1. Within these PcG domains we observe increased H3-K9 methylation. Finally, we show that H3-K9 HMTase activity is associated with endogenous HPC2. Our findings suggest a role for the SUV39H1 HMTase and histone H3-K9 methylation in the targeting of human HPC/HPH PcG proteins to modified chromatin structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Cell Nucleus / metabolism
  • Centromere / metabolism
  • Chromosomes / metabolism*
  • Chromosomes, Human, Pair 1 / metabolism
  • HeLa Cells
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histones / metabolism*
  • Humans
  • Ligases
  • Macromolecular Substances
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Polycomb-Group Proteins
  • Precipitin Tests
  • Protein Binding / physiology
  • Protein Structure, Tertiary / physiology
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / classification
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Ubiquitin-Protein Ligases

Substances

  • Histones
  • Macromolecular Substances
  • Polycomb-Group Proteins
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • SUV39H1 protein, human
  • Methyltransferases
  • Histone-Lysine N-Methyltransferase
  • Ubiquitin-Protein Ligases
  • Ligases
  • CBX4 protein, human