School of Applied and Engineering Physics, Cornell University, Ithaca, New York.
School of Molecular Biosciences, Washington State University, Pullman, Washington.
Biophys J. 2018 Sep 4;115(5):773-781. doi: 10.1016/j.bpj.2018.07.009. Epub 2018 Jul 31.
DNA is tightly wrapped around histone proteins in nucleosome core particles (NCPs) yet must become accessible for processing in the cell. This accessibility, a key component of transcription regulation, is influenced by the properties of both the histone proteins and the DNA itself. Small angle x-ray scattering with contrast variation is used to examine how sequence variations affect DNA unwrapping from NCPs at different salt concentrations. Salt destabilizes NCPs, populating multiple unwrapped states as many possible unwrapping pathways are explored by the complexes. We apply coarse-grained Monte Carlo methods to generate realistic sequence-dependent unwrapped structures for the nucleosomal DNA with thermal variations. An ensemble optimization method is employed to determine the composition of the overall ensemble as electrostatic interactions are weakened. Interesting DNA-sequence-dependent differences are revealed in the unwrapping paths and equilibrium constants. These differences are correlated with specific features within the nucleic acid sequences.
DNA 紧密缠绕在核小体核心颗粒（NCPs）中的组蛋白蛋白周围，但必须在细胞中变得可用于处理。这种可及性是转录调控的关键组成部分，受组蛋白蛋白和 DNA 本身特性的影响。利用小角 X 射线散射和对比度变化来研究序列变异如何在不同盐浓度下影响 NCP 中 DNA 的解缠绕。盐使 NCP 不稳定，当复合物探索许多可能的解缠绕途径时，会出现多种解缠绕状态。我们应用粗粒度的蒙特卡罗方法生成具有热变异性的核小体 DNA 的现实序列相关解缠绕结构。采用整体优化方法来确定整个集合的组成，因为静电相互作用减弱。在解缠绕路径和解离常数中发现了有趣的 DNA 序列依赖性差异。这些差异与核酸序列中的特定特征相关。
