Histone methyltransferase activity of a Drosophila Polycomb group repressor complex

Cell. 2002 Oct 18;111(2):197-208. doi: 10.1016/s0092-8674(02)00976-5.

Abstract

Polycomb group (PcG) proteins maintain transcriptional repression during development, likely by creating repressive chromatin states. The Extra Sex Combs (ESC) and Enhancer of Zeste [E(Z)] proteins are partners in an essential PcG complex, but its full composition and biochemical activities are not known. A SET domain in E(Z) suggests this complex might methylate histones. We purified an ESC-E(Z) complex from Drosophila embryos and found four major subunits: ESC, E(Z), NURF-55, and the PcG repressor, SU(Z)12. A recombinant complex reconstituted from these four subunits methylates lysine-27 of histone H3. Mutations in the E(Z) SET domain disrupt methyltransferase activity in vitro and HOX gene repression in vivo. These results identify E(Z) as a PcG protein with enzymatic activity and implicate histone methylation in PcG-mediated silencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone*
  • DNA-Binding Proteins / genetics
  • Drosophila / embryology
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / isolation & purification
  • Drosophila Proteins / metabolism*
  • Gene Silencing
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase*
  • Homeodomain Proteins*
  • Insect Proteins / isolation & purification
  • Lysine / metabolism
  • Methyltransferases / metabolism*
  • Molecular Chaperones*
  • Nuclear Proteins / isolation & purification
  • Nuclear Proteins / metabolism*
  • Polycomb Repressive Complex 1
  • Polycomb Repressive Complex 2
  • Protein Methyltransferases
  • Recombination, Genetic
  • Repressor Proteins / isolation & purification
  • Repressor Proteins / metabolism*
  • Retinoblastoma-Binding Protein 4
  • Transcription Factors*

Substances

  • Caf1-55 protein, Drosophila
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Homeodomain Proteins
  • Insect Proteins
  • Molecular Chaperones
  • Nuclear Proteins
  • Pc protein, Drosophila
  • Repressor Proteins
  • Retinoblastoma-Binding Protein 4
  • Su(z)12 protein, Drosophila
  • Transcription Factors
  • Ubx protein, Drosophila
  • Histone Methyltransferases
  • Methyltransferases
  • Protein Methyltransferases
  • E(z) protein, Drosophila
  • Histone-Lysine N-Methyltransferase
  • Polycomb Repressive Complex 2
  • esc protein, Drosophila
  • Polycomb Repressive Complex 1
  • Lysine