Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.
Electrostatic mechanism of nucleosomal array folding revealed by computer simulation.
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DOI：
10.1073/pnas.0408867102
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发表时间：
2005-06
影响因子：
11.1
通讯作者：
Jian Sun;Qing Zhang;T. Schlick
中科院分区：
文献类型：
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作者：
Jian Sun;Qing Zhang;T. Schlick
尽管大量实验表明染色质纤维具有依赖于盐的构象，但其相关的分子机制仍不清楚。在这里，我们应用包含所有组蛋白尾巴的核小体的不规则离散表面电荷优化(DISCO)模型，通过蒙特卡罗模拟来描述具有12个核小体的核小体阵列的盐依赖重排。核小体阵列构象的整体表现出与盐相关的凝聚，这与流体动力学测量结果很好地一致，并表明该阵列在高(生理)盐浓度下采用高度不规则的3D之字形构象，在低盐浓度下转变为扩展的“串上珠”构象。能量分析表明，连接体DNA之间的排斥导致了这种扩展形式，而核小体间的吸引推动了高盐下的折叠。这两种贡献之间的平衡决定了依赖于盐的凝聚。重要的是，核小体间和连接子DNA-核小体的吸引需要组蛋白尾巴；我们发现，尤其是H3尾巴，对于在生理单价盐中稳定适度折叠的纤维至关重要。
Although numerous experiments indicate that the chromatin fiber displays salt-dependent conformations, the associated molecular mechanism remains unclear. Here, we apply an irregular Discrete Surface Charge Optimization (DiSCO) model of the nucleosome with all histone tails incorporated to describe by Monte Carlo simulations salt-dependent rearrangements of a nucleosomal array with 12 nucleosomes. The ensemble of nucleosomal array conformations display salt-dependent condensation in good agreement with hydrodynamic measurements and suggest that the array adopts highly irregular 3D zig-zag conformations at high (physiological) salt concentrations and transitions into the extended "beads-on-a-string" conformation at low salt. Energy analyses indicate that the repulsion among linker DNA leads to this extended form, whereas internucleosome attraction drives the folding at high salt. The balance between these two contributions determines the salt-dependent condensation. Importantly, the internucleosome and linker DNA-nucleosome attractions require histone tails; we find that the H3 tails, in particular, are crucial for stabilizing the moderately folded fiber at physiological monovalent salt.