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The Dynamic Influence of Linker Histone Saturation within the Poly-Nucleosome Array
bioRxiv - Biophysics Pub Date : 2020-09-21 , DOI: 10.1101/2020.09.20.305581
Dustin C. Woods , Francisco Rodríguez-Ropero , Jeff Wereszczynski

Linker histones bind to nucleosomes and modify chromatin structure and dynamics as a means of epigenetic regulation. Biophysical studies have shown that chromatin fibers can adopt a plethora of conformations with varying levels of compaction. Linker histone condensation, and its specific binding disposition, has been associated with directly tuning this ensemble of states. However, the atomistic dynamics and quantification of this mechanism remains poorly understood. Here, we present molecular dynamics simulations of octa-nucleosome arrays, based on a cryo-EM structure of the 30-nm chromatin fiber, with and without the globular domains of the H1 linker histone to determine how they influence fiber structures and dynamics. Results show that when bound, linker histones inhibit DNA flexibility and stabilize repeating tetra-nucleosomal units, giving rise to increased chromatin compaction. Furthermore, upon the removal of H1, there is a significant destabilization of this compact structure as the fiber adopts less strained and untwisted states. Interestingly, linker DNA sampling in the octa-nucleosome is exaggerated compared to its mono-nucleosome counterparts, suggesting that chromatin architecture plays a significant role in DNA strain even in the absence of linker histones. Moreover, H1-bound states are shown to have increased stiffness within tetra-nucleosomes, but not between them. This increased stiffness leads to stronger long-range correlations within the fiber, which may result in the propagation of epigenetic signals over longer spatial ranges. These simulations highlight the effects of linker histone binding on the internal dynamics and global structure of poly-nucleosome arrays, while providing physical insight into a mechanism of chromatin compaction.

中文翻译:

多核糖体阵列中接头组蛋白饱和度的动态影响

接头组蛋白与核小体结合并修饰染色质结构和动力学,作为表观遗传调控的手段。生物物理研究表明,染色质纤维可以采用多种构象,具有不同的紧实度。接头组蛋白缩合及其特定的结合方式与直接调节这种状态有关。但是,这种机制的原子动力学和量化仍然知之甚少。在这里,我们介绍了基于30 nm染色质纤维的冷冻EM结构,有无H1接头组蛋白的球状结构域的八核小体阵列的分子动力学模拟,以确定它们如何影响纤维结构和动力学。结果表明,结合后,接头组蛋白抑制DNA柔性并稳定重复的四核小体单元,导致染色质紧实度增加。此外,在除去H1时,由于纤维采用较小的应变和未加捻状态,因此这种紧密结构的稳定性显着下降。有趣的是,与单核小体对应物相比,八核小体中的接头DNA采样被夸大了,这表明即使在没有接头组蛋白的情况下,染色质结构在DNA菌株中也起着重要作用。而且,H1结合态显示出在四核小体中具有增加的刚度,但在它们之间没有。这种增加的刚度导致光纤内更强的远程相关性,这可能导致表观遗传信号在更长的空间范围内传播。
更新日期:2020-09-22
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