Exploring the Free Energy Landscape of Nucleosomes
Exploring the Free Energy Landscape of Nucleosomes
复制标题
DOI：
10.1021/jacs.6b02893
复制
发表时间：
2016-07-06
影响因子：
15
通讯作者：
Wolynes, Peter G.
中科院分区：
文献类型：
--
作者：
Zhang, Bin;Zheng, Weihua;Wolynes, Peter G.
核小体是包装基因组的基本单位。一个详细的分子图像，其构象动力学是至关重要的理解转录和基因调控。我们研究单个核小体的拆卸使用可转移力场的预测粗粒度蛋白质DNA模型。该模型定量描述了组蛋白核心复合物和核小体的热力学稳定性，并预测了与实验测量相匹配的瞬时核小体开放率。自由能景观的定量表征揭示了核小体解折叠的机制，其中DNA解折叠和组蛋白解体是耦合的。当核小体打开时，H2 A-H2 B二聚体和（H3-H4）（2）四聚体之间的界面首先丢失，释放大部分但不是全部的结合DNA。对于单分子实验中研究的短链，DNA从组蛋白中不对称地解旋，只有其两端中的一端优先暴露。详细的分子机制，揭示了这项工作提供了一个结构基础，解释核小体去折叠的实验研究。
The nucleosome is the fundamental unit for packaging the genome. A detailed molecular picture for its conformational dynamics is crucial for understanding transcription and gene regulation. We investigate the disassembly of single nucleosomes using a predictive coarse-grained protein DNA model with transferable force fields. This model quantitatively describes the thermodynamic stability of both the histone core complex and the nucleosome and predicts rates of transient nucleosome opening that match experimental measurements. Quantitative characterization of the free-energy landscapes reveals the mechanism of nucleosome unfolding in which DNA unwinding and histone protein disassembly are coupled. The interfaces between H2A-H2B dimers and the (H3-H4)(2) tetramer are first lost when the nucleosome opens releasing a large fraction but not all of its bound DNA. For the short strands studied in single molecule experiments, the DNA unwinds asymmetrically from the histone proteins, with only one of its two ends preferentially exposed. The detailed molecular mechanism revealed in this work provides a structural basis for interpreting experimental studies of nucleosome unfolding.