Progressive methylation of ageing histones by Dot1 functions as a timer
Progressive methylation of ageing histones by Dot1 functions as a timer
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DOI：
10.1038/embor.2011.131
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发表时间：
2011-09-01
期刊：
影响因子：
7.7
通讯作者：
van Leeuwen, Fred
中科院分区：
文献类型：
--
作者：
De Vos, Dirk;Frederiks, Floor;van Leeuwen, Fred
组蛋白的翻译后修饰在调控基因表达中具有重要作用。如果在染色体复制后有效地重建，组蛋白修饰可以通过表观遗传机制帮助繁殖分裂细胞中的基因表达模式。我们使用了一种综合的方法来研究组蛋白H3 Lys 79（H3K79）的保守甲基化的动力学Dot1。我们的研究结果表明，甲基化的H3K79组蛋白沉积后进行性变化，这是不兼容的快速复制机制。相反，甲基化在老化的组蛋白上积累，为细胞提供计时器机制，将细胞周期长度直接与核小体核心染色质修饰的变化结合起来。
Post-translational modifications of histone proteins have a crucial role in regulating gene expression. If efficiently re-established after chromosome duplication, histone modifications could help propagate gene expression patterns in dividing cells by epigenetic mechanisms. We used an integrated approach to investigate the dynamics of the conserved methylation of histone H3 Lys 79 (H3K79) by Dot1. Our results show that methylation of H3K79 progressively changes after histone deposition, which is incompatible with a rapid copy mechanism. Instead, methylation accumulates on ageing histones, providing the cell with a timer mechanism to directly couple cell-cycle length to changes in chromatin modification on the nucleosome core.