Abstract
E2F-6 contributes to gene silencing in a manner independent of retinoblastoma protein family members. To better elucidate the molecular mechanism of repression by E2F-6, we have purified the factor from cultured cells. E2F-6 is found in a multimeric protein complex that contains Mga and Max, and thus the complex can bind not only to the E2F-binding site but also to Myc- and Brachyury-binding sites. Moreover, the complex contains chromatin modifiers such as a novel histone methyltransferase that modifies lysine 9 of histone H3, HP1gamma, and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G0 cells rather than in G1 cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Binding Sites
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Cell Cycle Proteins*
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Chromatin / metabolism*
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Chromobox Protein Homolog 5
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Chromosomal Proteins, Non-Histone / metabolism
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DNA-Binding Proteins*
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Dimerization
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E2F Transcription Factors
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E2F6 Transcription Factor
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G1 Phase
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Gene Silencing*
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HeLa Cells
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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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Mass Spectrometry
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Methylation
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Methyltransferases / chemistry
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Methyltransferases / metabolism
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Molecular Sequence Data
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Phosphoproteins / metabolism
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Promoter Regions, Genetic*
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Protein Footprinting
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Protein Methyltransferases
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Proteins*
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Proto-Oncogene Proteins c-myc / metabolism
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Recombinant Proteins / metabolism
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Resting Phase, Cell Cycle*
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Retinoblastoma-Like Protein p130
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Transcription Factors / chemistry
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Transcription Factors / isolation & purification
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Transcription Factors / metabolism*
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Transcription, Genetic*
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Two-Hybrid System Techniques
Substances
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Cell Cycle Proteins
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Chromatin
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Chromosomal Proteins, Non-Histone
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DNA-Binding Proteins
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E2F Transcription Factors
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E2F6 Transcription Factor
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E2F6 protein, human
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Histones
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins c-myc
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RBL2 protein, human
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Recombinant Proteins
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Retinoblastoma-Like Protein p130
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Transcription Factors
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Chromobox Protein Homolog 5
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EHMT1 protein, human
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Histone Methyltransferases
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Methyltransferases
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Protein Methyltransferases
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Histone-Lysine N-Methyltransferase