Université Paris-Saclay, ENS Paris-Saclay, CNRS, Laboratoire de biologie et pharmacologie appliquée, 61 avenue du Président Wilson, 94235 Cachan cedex, France.
51 Natal Road, Cambridge CB1 3NY, UK.
J Struct Biol. 2020 Jul 1;211(1):107511. doi: 10.1016/j.jsb.2020.107511. Epub 2020 Apr 18.
Most of eukaryotic cellular DNA is packed in nucleosome core particles (NCPs), in which the DNA (DNA) is wrapped around histones. The influence of this organization on the intrinsic local dynamics of DNA is largely unknown, in particular because capturing such information from experiments remains notoriously challenging. Given the importance of dynamical properties in DNA functions, we addressed this issue using CHARMM36 MD simulations of a nucleosome containing the NCP positioning 601 sequence and four related free dodecamers. Comparison between DNA and free DNA reveals a limited impact of the dense DNA-histone interface on correlated motions of dinucleotide constituents and on fluctuations of inter base pair parameters. A characteristic feature intimately associated with the DNA super-helical path is a set of structural periodicities that includes a marked alternation of regions enriched in backbone BI and BII conformers. This observation led to uncover a convincing correspondence between the sequence effect on BI/BII propensities in both DNA and free DNA, strengthening the idea that the histone preference for particular DNA sequences relies on those intrinsic structural properties. These results offer for the first time a detailed view of the DNA dynamical behavior within NCP. They show in particular that the DNA dynamics is substantial enough to preserve the ability to structurally adjust to external proteins, for instance remodelers. Also, fresh structural arguments highlight the relevance of relationships between DNA sequence and structural properties for NCP formation. Overall, our work offers a more rational framework to approach the functional, biological roles of NCP.
真核细胞的大部分 DNA 都被包装在核小体核心颗粒（NCPs）中，其中 DNA（脱氧核糖核酸）缠绕在组蛋白周围。这种组织对 DNA 固有局部动力学的影响在很大程度上是未知的，特别是因为从实验中捕捉到这种信息仍然极具挑战性。鉴于动力学特性在 DNA 功能中的重要性，我们使用包含 NCP 定位 601 序列和四个相关自由十二聚体的核小体的 CHARMM36 MD 模拟来解决这个问题。将 DNA 与自由 DNA 进行比较，发现致密的 DNA-组蛋白界面对二核苷酸成分的相关运动和碱基对参数的波动的影响有限。与 DNA 超螺旋路径密切相关的一个特征是一组结构周期性，其中包括富含骨干 BI 和 BII 构象的区域的明显交替。这一观察结果导致在 DNA 和自由 DNA 中揭示了序列对 BI/BII 倾向的影响之间存在令人信服的对应关系，这加强了组蛋白对特定 DNA 序列的偏好依赖于这些内在结构特性的观点。这些结果首次提供了 NCP 内 DNA 动力学行为的详细视图。它们特别表明，DNA 动力学足够大，可以保持结构上适应外部蛋白质（例如重塑因子）的能力。此外，新的结构论据突出了 DNA 序列和结构特性之间的关系对 NCP 形成的相关性。总的来说，我们的工作为研究 NCP 的功能和生物学作用提供了一个更合理的框架。
