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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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HeLa Cells
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Histone Deacetylase 1
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase*
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Histones / metabolism
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Humans
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Lysine / metabolism
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Macromolecular Substances
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Methyltransferases / genetics
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Methyltransferases / metabolism*
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Molecular Sequence Data
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Multiprotein Complexes
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Polycomb Repressive Complex 1
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Polycomb Repressive Complex 2
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Protein Methyltransferases
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Retinoblastoma-Binding Protein 4
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Retinoblastoma-Binding Protein 7
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Sequence Homology, Amino Acid
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Substrate Specificity
Substances
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Carrier Proteins
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Drosophila Proteins
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Histones
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Macromolecular Substances
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Multiprotein Complexes
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Nuclear Proteins
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Pc protein, Drosophila
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RBBP4 protein, human
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RBBP7 protein, human
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Rbbp4 protein, mouse
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Repressor Proteins
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Retinoblastoma-Binding Protein 4
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Retinoblastoma-Binding Protein 7
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Su(z)12 protein, Drosophila
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Histone Methyltransferases
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Methyltransferases
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Protein Methyltransferases
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E(z) protein, Drosophila
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Histone-Lysine N-Methyltransferase
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PRC2 protein, Drosophila
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Polycomb Repressive Complex 2
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esc protein, Drosophila
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Polycomb Repressive Complex 1
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HDAC1 protein, human
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Histone Deacetylase 1
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Histone Deacetylases
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Lysine