A quantitative model of nucleosome dynamics
A quantitative model of nucleosome dynamics
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DOI：
10.1093/nar/gkr422
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发表时间：
2011-10-01
影响因子：
14.9
通讯作者：
Bundschuh, Ralf
中科院分区：
文献类型：
--
作者：
Forties, Robert A.;North, Justin A.;Bundschuh, Ralf
真核生物基因组的表达、复制和修复需要染色质的基本组织单位--核小体被解开和分解。我们已经开发了一个核小体动力学的定量模型，它提供了这些DNA过程的基本理解。我们使用高精度单分子核小体解压缩实验的结果校准了该模型，然后测试了其对核小体被DNA错配识别复合物hMSH 2-hMSH 6分解的实验的预测。我们发现，这个校准模型定量描述hMSH 2-hMSH 6诱导的核小体解体率与两个单独的DNA序列和四个不同的组蛋白修饰状态。此外，该模型提供了hMSH 2-hMSH 6的核小体解体机制的见解和组蛋白修饰对这种解体反应的影响。该模型与当前实验的精确一致性表明，它可以更普遍地应用于对DNA加工过程中发生的众多核小体改变提供重要的机械理解。
The expression, replication and repair of eukaryotic genomes require the fundamental organizing unit of chromatin, the nucleosome, to be unwrapped and disassembled. We have developed a quantitative model of nucleosome dynamics which provides a fundamental understanding of these DNA processes. We calibrated this model using results from high precision single molecule nucleosome unzipping experiments, and then tested its predictions for experiments in which nucleosomes are disassembled by the DNA mismatch recognition complex hMSH2-hMSH6. We found that this calibrated model quantitatively describes hMSH2-hMSH6 induced disassembly rates of nucleosomes with two separate DNA sequences and four distinct histone modification states. In addition, this model provides mechanistic insight into nucleosome disassembly by hMSH2-hMSH6 and the influence of histone modifications on this disassembly reaction. This model's precise agreement with current experiments suggests that it can be applied more generally to provide important mechanistic understanding of the numerous nucleosome alterations that occur during DNA processing.