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Histone methyltransferase activity of a Drosophila Polycomb group repressor complex.

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.

Pubmed ID: 12408864


  • Müller J
  • Hart CM
  • Francis NJ
  • Vargas ML
  • Sengupta A
  • Wild B
  • Miller EL
  • O'Connor MB
  • Kingston RE
  • Simon JA



Publication Data

October 18, 2002

Associated Grants


Mesh Terms

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