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
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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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Animals
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Chromosomal Proteins, Non-Histone*
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DNA-Binding Proteins / genetics
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Drosophila / embryology
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Drosophila / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / isolation & purification
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Drosophila Proteins / metabolism*
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Gene Silencing
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Histone Methyltransferases
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Histone-Lysine N-Methyltransferase*
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Homeodomain Proteins*
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Insect Proteins / isolation & purification
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Lysine / metabolism
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Methyltransferases / metabolism*
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Molecular Chaperones*
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Nuclear Proteins / isolation & purification
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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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Recombination, Genetic
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Repressor Proteins / isolation & purification
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Repressor Proteins / metabolism*
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Retinoblastoma-Binding Protein 4
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Transcription Factors*
Substances
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Caf1-55 protein, Drosophila
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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Drosophila Proteins
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Homeodomain Proteins
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Insect Proteins
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Molecular Chaperones
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Nuclear Proteins
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Pc protein, Drosophila
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Repressor Proteins
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Retinoblastoma-Binding Protein 4
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Su(z)12 protein, Drosophila
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Transcription Factors
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Ubx 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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Polycomb Repressive Complex 2
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esc protein, Drosophila
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Polycomb Repressive Complex 1
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Lysine