Centre for Biological Signalling Studies (BIOSS) and Centre for Integrative Biological Signalling Studies (CIBSS), University of Freiburg, 79104 Freiburg, Germany; email:
Molecular and Cellular Modeling Group, Heidelberg Institute for Theoretical Studies (HITS), 69118 Heidelberg, Germany; email:
Annu Rev Phys Chem. 2020 Apr 20;71:101-119. doi: 10.1146/annurev-physchem-071119-040043. Epub 2020 Feb 4.
Chromatosomes are fundamental units of chromatin structure that are formed when a linker histone protein binds to a nucleosome. The positioning of the linker histone on the nucleosome influences the packing of chromatin. Recent simulations and experiments have shown that chromatosomes adopt an ensemble of structures that differ in the geometry of the linker histone-nucleosome interaction. In this article we review the application of Brownian, Monte Carlo, and molecular dynamics simulations to predict the structure of linker histone-nucleosome complexes, to study the binding mechanisms involved, and to predict how this binding affects chromatin fiber structure. These simulations have revealed the sensitivityof the chromatosome structure to variations in DNA and linker histone sequence, as well as to posttranslational modifications, thereby explaining the structural variability observed in experiments. We propose that a concerted application of experimental and computational approaches will reveal the determinants of chromatosome structural variability and how it impacts chromatin packing.
染色质小体是染色质结构的基本单位，当连接组蛋白结合到核小体时形成。连接组蛋白在核小体上的定位影响染色质的包装。最近的模拟和实验表明，染色质小体采用了一系列结构，这些结构在连接组蛋白-核小体相互作用的几何形状上有所不同。在本文中，我们综述了布朗运动、蒙特卡罗和分子动力学模拟在预测连接组蛋白-核小体复合物结构、研究相关结合机制以及预测这种结合如何影响染色质纤维结构中的应用。这些模拟揭示了染色质小体结构对 DNA 和连接组蛋白序列以及翻译后修饰变化的敏感性，从而解释了实验中观察到的结构可变性。我们提出，综合应用实验和计算方法将揭示染色质小体结构可变性的决定因素及其对染色质包装的影响。
