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A Viral Mechanism for Remodeling Chromatin Structure in G_0 Cells

机译:重塑G_0细胞中染色质结构的病毒机制

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Small DNA viruses force quiescent cells to reenter the cell cycle in order to replicate their DNA. we report here that the adenovirus E1A protein creates an S phase environment in quiescent cells by overcoming the nucleosomal repression of E2F-targeted genes. These genes are surrounded by Lys-9-methylated H3 histones, and their promoters are occupied by the pRb-related protein p130 and the inhibitory transcription factor E2F4. Kinetic analysis indicates that E1A binds to E2F promoters where it eliminates p130 and E2F4, resulting in the dramatic elimination of H3 Lys-9 methylation. Thereafter, H3 Lys-9 acetylation occurs along with the recruitment of activating E2F family members, and this is followed by the transcriptional activity of E2F-targeted genes. These results indicate that E1A has a role in reconfiguring chromatin structure and that this activity is necessary to overcome the repressive mechanisms that maintain cells in a quiescent state.
机译:小型DNA病毒迫使静止的细胞重新进入细胞周期,以复制其DNA。我们在此报告,腺病毒E1A蛋白通过克服E2F靶向基因的核小体抑制,在静止细胞中创建了S期环境。这些基因被Lys-9-甲基化的H3组蛋白包围,其启动子被pRb相关蛋白p130和抑制性转录因子E2F4占据。动力学分析表明,E1A与E2F启动子结合,从而消除了p130和E2F4,从而显着消除了H3 Lys-9甲基化。此后,H3 Lys-9乙酰化与激活的E2F家族成员的募集一起发生,然后是E2F靶向基因的转录活性。这些结果表明,E1A在重新配置染色质结构中具有作用,并且该活性对于克服将细胞维持在静止状态的抑制机制是必需的。

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