Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein

  1. Andrei Kuzmichev1,
  2. Kenichi Nishioka1,
  3. Hediye Erdjument-Bromage2,
  4. Paul Tempst2, and
  5. Danny Reinberg1,3
  1. 1Howard Hughes Medical Institute, Division of Nucleic Acids Enzymology, Department of Biochemistry, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA; 2Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA

Abstract

Enhancer of Zeste [E(z)] is a Polycomb-group transcriptional repressor and one of the founding members of the family of SET domain-containing proteins. Several SET-domain proteins possess intrinsic histone methyltransferase (HMT) activity. However, recombinant E(z) protein was found to be inactive in a HMT assay. Here we report the isolation of a multiprotein E(z) complex that contains extra sex combs, suppressor of zeste-12 [Su(z)12], and the histone binding proteins RbAp46/RbAp48. This complex, which we termed Polycomb repressive complex (PRC) 2, possesses HMT activity with specificity for Lys 9 (K9) and Lys 27 (K27) of histone H3. The HMT activity of PRC2 is dependent on an intact SET domain in the E(z) protein. We hypothesize that transcriptional repression by the E(z) protein involves methylation-dependent recruitment of PRC1. The presence of Su(z)12, a strong suppressor of position effect variegation, in PRC2 suggests that PRC2 may play a widespread role in heterochromatin-mediated silencing.

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Footnotes

  • 3 Corresponding author.

  • E-MAIL reinbedf{at}umdnj.edu; FAX (732) 235-5294.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1035902.

    • Received August 23, 2002.
    • Accepted September 23, 2002.
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