The Dynamic Influence of Linker Histone Saturation within the Poly-Nucleosome Array.
The Dynamic Influence of Linker Histone Saturation within the Poly-Nucleosome Array.
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DOI：
10.1016/j.jmb.2021.166902
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发表时间：
2021-05-14
影响因子：
5.6
通讯作者：
Wereszczynski J
中科院分区：
文献类型：
--
作者：
Woods DC;Rodríguez-Ropero F;Wereszczynski J
作为一种表观遗传调控手段，连接蛋白结合核小体并修饰染色质结构和动力学。生物物理学研究表明，染色质纤维可以采用不同程度的压实过多的构象。连接体组蛋白缩合及其特定的结合配置与直接调节这种状态集合有关。然而，这一机制的原子动力学和量化仍然知之甚少。在这里，我们基于30纳米染色质纤维的低温电镜结构，对八核小体阵列进行了分子动力学模拟，以确定H1连接蛋白的球状结构域如何影响纤维结构和动力学。结果表明，当连接蛋白结合时，连接蛋白抑制DNA的柔韧性并稳定重复的四核体单元，从而增加染色质压实。此外，在去除H1后，由于纤维采用较少的应变和未扭曲状态，这种致密结构存在显着的不稳定性。有趣的是，与单核小体相比，八核小体中的连接子DNA采样被夸大了，这表明即使在没有连接子组蛋白的情况下，染色质结构在DNA菌株中也起着重要作用。此外，h1结合态在四核小体内部的硬度增加，而在四核小体之间则没有增加。这种增加的刚度导致纤维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。这些模拟突出了连接体组蛋白结合对多核小体阵列内部动力学和整体结构的影响，同时为染色质压实机制提供了物理见解。
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.
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影响因子：
3.5
作者：
Alkhatib SG;Landry JW
通讯作者：
Landry JW
DOI：
10.1073/pnas.0810057105
发表时间：
2008-12-16
影响因子：
11.1
作者：
Eltsov, Mikhail;MacLellan, Kirsty M.;Dubochet, Jacques
通讯作者：
Dubochet, Jacques
影响因子：
3.3
作者：
Cai S;Böck D;Pilhofer M;Gan L
通讯作者：
Gan L
DOI：
10.1073/pnas.1315872111
发表时间：
2014-06-03
影响因子：
11.1
作者：
Collepardo-Guevara, Rosana;Schlick, Tamar
通讯作者：
Schlick, Tamar
影响因子：
56.9
作者：
Dorigo, B;Schalch, T;Richmond, TJ
通讯作者：
Richmond, TJ