Lysine Acetylation Facilitates Spontaneous DNA Dynamics in the Nucleosome.
Lysine Acetylation Facilitates Spontaneous DNA Dynamics in the Nucleosome.
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DOI：
10.1021/acs.jpcb.5b09734
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发表时间：
2015-12-03
期刊：
影响因子：
--
通讯作者：
Lee TH
中科院分区：
文献类型：
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作者：
Kim J;Lee J;Lee TH
核小体由一个被DNA包裹的组蛋白核心组成，是细胞中DNA的基本包装单位。组蛋白核心的赖氨酸乙酰化提高了核小体中DNA的可及性，其机制在很大程度上仍不清楚。通过使用我们最近开发的杂交单分子方法，我们在这里报告了组蛋白H3赖氨酸56(H3K56)的乙酰化如何改变核小体中DNA的结构动力学，这是提高DNA可及性的关键。我们的结果表明，H3K56乙酰化促进了核小体末端DNA的结构动力学，该结构在ms时间尺度上自发地重复打开和关闭。这些结果支持组蛋白乙酰化在催化DNA解包中的分子机制，其效率最终受到核小体模板上的自发DNA动力学的限制。这项研究提供了第一个也是唯一的实验证据，揭示了蛋白质化学修饰在直接调节DNA包装单元的动力学稳定性方面的作用。
The nucleosome, comprising a histone protein core wrapped around by DNA, is the fundamental packing unit of DNA in cells. Lysine acetylation at the histone core elevates DNA accessibility in the nucleosome, the mechanism of which remains largely unknown. By employing our recently developed hybrid single molecule approach, here we report how the structural dynamics of DNA in the nucleosome is altered upon acetylation at histone H3 lysine 56 (H3K56) that is critical for elevated DNA accessibility. Our results indicate that H3K56 acetylation facilitates the structural dynamics of the DNA at the nucleosome termini that spontaneously and repeatedly open and close on a ms time scale. The results support a molecular mechanism of histone acetylation in catalyzing DNA unpacking whose efficiency is ultimately limited by the spontaneous DNA dynamics at the nucleosome temini. This study provides the first and unique experimental evidence revealing a role of protein chemical modification in directly regulating the kinetic stability of the DNA packing unit.