Armeev Grigoriy A, Moiseenko Andrey V, Motorin Nikita A, Afonin Dmitriy A, Zhao Lei, Vasilev Veniamin A, Oleinikov Pavel D, Glukhov Grigory S, Peters Georgy S, Studitsky Vasily M, Feofanov Alexey V, Shaytan Alexey K, Shi Xiangyan, Sokolova Olga S
Department of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Department of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.
Structure. 2025 May 1;33(5):948-959.e5. doi: 10.1016/j.str.2025.02.007. Epub 2025 Mar 17.
Nucleosomes are fundamental elements of chromatin organization that participate in compacting genomic DNA and serve as targets for the binding of numerous regulatory proteins. Currently, over 500 different nucleosome structures are known. Despite the large number of nucleosome structures, all of them were formed on only about twenty different DNA sequences. Using cryo-electron microscopy, we determined the structure of the nucleosome formed on a high-affinity Widom 603 DNA sequence at 4 Å resolution; an atomic model was built. We proposed an integrative modeling approach to study the nucleosomal DNA unwrapping based on the cryoelectron microscopy (cryo-EM) data. We also demonstrated the DNA unwrapping of the Widom 603 nucleosome using small angle X-ray scattering and single particle Förster resonance energy transfer measurements. Our results are consistent with the asymmetry of nucleosomal DNA unwrapping. Our data revealed the dependence of nucleosome structure and dynamics on the sequence of nucleosomal DNA.
核小体是染色质组织的基本元件，参与压缩基因组DNA，并作为众多调控蛋白结合的靶点。目前，已知有500多种不同的核小体结构。尽管核小体结构数量众多，但它们都是在仅约20种不同的DNA序列上形成的。利用冷冻电子显微镜，我们在4埃分辨率下确定了在高亲和力的维德姆603 DNA序列上形成的核小体的结构；构建了一个原子模型。我们提出了一种基于冷冻电子显微镜（cryo-EM）数据研究核小体DNA解旋的综合建模方法。我们还利用小角X射线散射和单颗粒荧光共振能量转移测量证明了维德姆603核小体的DNA解旋。我们的结果与核小体DNA解旋的不对称性一致。我们的数据揭示了核小体结构和动力学对核小体DNA序列的依赖性。
