Science · 2002 · 767 citations · 11 references
Life SciencesGeneticsMolecular BiologyChromatin BiologyGene ExpressionTranscriptional RegulationChromatinChromatin InteractionsHistone ModificationsHistone ProteinsPolycomb RegulationPromoter RegulationE2f Transcription ControlE2f Transcription FactorsPolycomb Group ProteinsPolycomb Group RegulationPolycomb Group RepressionPolycomb-mediated RepressionPromotersRetinoblastoma Family Proteins
E2F-6 contributes to gene silencing independently of retinoblastoma family members. The study aims to elucidate the molecular mechanism of E2F-6–mediated repression by purifying the factor from cultured cells. The authors purified E2F-6 from cultured cells to investigate its repression mechanism. E2F-6 forms a multimeric complex with Mga, Max, and chromatin modifiers—including a novel H3K9 methyltransferase, HP1γ, and Polycomb proteins—that binds E2F, Myc, and Brachyury sites and preferentially occupies target promoters in G0 cells, suggesting these modifiers silence E2F- and Myc-responsive genes in quiescent cells.
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, HP1γ, and Polycomb group (PcG) proteins. The E2F-6 complex preferentially occupies target promoters in G 0 cells rather than in G 1 cells. These data suggest that these chromatin modifiers contribute to silencing of E2F- and Myc-responsive genes in quiescent cells.
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Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain
Andrew J. Bannister, Philip Zegerman, Janet F. Partridge et al. · Nature · 2001 · 2.9K citations
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins
Monika Lachner, Dónal O’Carroll, Stephen Rea et al. · Nature · 2001 · 2.8K citations
Makoto Tachibana, Kenji Sugimoto, Tatsunobu Fukushima et al. · Journal of Biological Chemistry · 2001 · 775 citations · Full text