Torsional stress can regulate the unwrapping of two outer half superhelical turns of nucleosomal DNA
Torsional stress can regulate the unwrapping of two outer half superhelical turns of nucleosomal DNA
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DOI：
10.1073/pnas.2020452118
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发表时间：
2021-02-16
影响因子：
11.1
通讯作者：
Kono, Hidetoshi
中科院分区：
文献类型：
--
作者：
Ishida, Hisashi;Kono, Hidetoshi
扭转应力对核小体的结构和稳定性有重要影响。RNA聚合酶对染色质中的DNA施加扭转应力，并将DNA从核小体中解包以获得编码在DNA中的遗传信息。为了了解扭转应力如何影响核小体的稳定性，我们用全原子分子动力学模拟研究了扭转应力下核小体DNA两端的两个半超螺旋圈的解缠。解开DNA的自由能表明，使DNA过度扭曲的正应力促进了DNA的大规模不对称解开，而没有DNA的大延伸。在解缠绕期间，DNA的一端与H3和H2 A-H2 B解离，而DNA的另一端稳定地保持缠绕。详细的分析表明，这种不对称解离是由DNA在正应力下的几何形状和可弯曲性促进的。这种几何形状稳定了扭曲DNA的大沟与H3 α N-螺旋之间的相互作用，而拉直的DNA使与H2 A-H2 B的相互作用不稳定。在负应力下，DNA变得更加可弯曲和灵活，这有助于解开的DNA与八聚体在稳定状态下结合。因此，我们得出结论，扭转应力有一个显着的影响，通过DNA的固有性质的DNA和八聚体的亲和力，并可以改变调节蛋白的可及性。
Torsional stress has a significant impact on the structure and stability of the nucleosome. RNA polymerase imposes torsional stress on the DNA in chromatin and unwraps the DNA from the nucleosome to access the genetic information encoded in the DNA. To understand how the torsional stress affects the stability of the nucleosome, we examined the unwrapping of two half superhelical turns of nucleosomal DNA from either end of the DNA under torsional stress with all-atom molecular dynamics simulations. The free energies for unwrapping the DNA indicate that positive stress that overtwists DNA facilitates a large-scale asymmetric unwrapping of the DNA without a large extension of the DNA. During the unwrapping, one end of the DNA was dissociated from H3 and H2A-H2B, while the other end of the DNA stably remained wrapped. The detailed analysis indicates that this asymmetric dissociation is facilitated by the geometry and bendability of the DNA under positive stress. The geometry stabilized the interaction between the major groove of the twisted DNA and the H3 alpha N-helix, and the straightened DNA destabilized the interaction with H2A-H2B. Under negative stress, the DNA became more bendable and flexible, which facilitated the binding of the unwrapped DNA to the octamer in a stable state. Consequently, we conclude that the torsional stress has a significant impact on the affinity of the DNA and the octamer through the inherent nature of the DNA and can change the accessibility of regulatory proteins.