title: Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein.
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.
authors.affiliation: Howard 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.
authors.forename: Andrei
authors.initials: A
authors.lastname: Kuzmichev
authors.forename: Kenichi
authors.initials: K
authors.lastname: Nishioka
authors.forename: Hediye
authors.initials: H
authors.lastname: Erdjument-Bromage
authors.forename: Paul
authors.initials: P
authors.lastname: Tempst
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D046911:Macromolecular Substances; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063151:Polycomb Repressive Complex 2; D011496:Protein Methyltransferases; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D006657:Histones; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; C066770:Pc protein, Drosophila; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; C489969:Rbbp4 protein, mouse; D012097:Repressor Proteins; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; C543390:Su(z)12 protein, Drosophila; D000076983:Histone Methyltransferases; D008780:Methyltransferases; D011496:Protein Methyltransferases; C083329:E(z) protein, Drosophila; D011495:Histone-Lysine N-Methyltransferase; C524066:PRC2 protein, Drosophila; D063151:Polycomb Repressive Complex 2; C543389:esc protein, Drosophila; D063150:Polycomb Repressive Complex 1; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases; D008239:Lysine