Structural Studies of Overlapping Dinucleosomes in Solution
Structural Studies of Overlapping Dinucleosomes in Solution
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DOI：
10.1016/j.bpj.2019.12.010
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发表时间：
2020-05-05
影响因子：
3.4
通讯作者：
Kono, Hidetoshi
中科院分区：
文献类型：
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作者：
Matsumoto, Atsushi;Sugiyama, Masaaki;Kono, Hidetoshi
重叠二核小体是由一个六体和一个八体组成的结构，似乎是在核小体重塑因子(S)的推动下通过核小体碰撞形成的。在本研究中，通过小角X射线和中子散射(分别为SAXS和SANS)、计算机模拟和分子动力学模拟，研究了OLDN的溶液结构。从晶体结构出发，我们基于简正波分析生成了构象系综，并寻找了能够很好地再现SAXS和SANS散射曲线的构象。我们发现，晶体结构中没有观察到的组蛋白尾巴的包含极大地提高了模型的质量。所获得的结构模型表明，OLDN具有由位于六体和八体之间的界面上的组蛋白尾部稳定的各种构象，同时与六体和八体DNA结合。此外，我们的模型定义了构象变化或动力学的可能方向，这可能为我们进一步理解染色质动力学在基因调控中的作用提供重要信息。
An overlapping dinucleosome (OLDN) is a structure composed of one hexasome and one octasome and appears to be formed through nucleosome collision promoted by nucleosome remodeling factor(s). In this study, the solution structure of the OLDN was investigated through the integration of small-angle x-ray and neutron scattering (SAXS and SANS, respectively), computer modeling, and molecular dynamics simulations. Starting from the crystal structure, we generated a conformational ensemble based on normal mode analysis and searched for the conformations that reproduced the SAXS and SANS scattering curves well. We found that inclusion of histone tails, which are not observed in the crystal structure, greatly improved model quality. The obtained structural models suggest that OLDNs adopt a variety of conformations stabilized by histone tails situated at the interface between the hexasome and octasome, simultaneously binding to both the hexasomal and octasomal DNA. In addition, our models define a possible direction for the conformational changes or dynamics, which may provide important information that furthers our understanding of the role of chromatin dynamics in gene regulation.