Nucleosomes, the building blocks of chromosomes, are also transcription regulators. Single molecule pulling experiments have shown that nucleosomes unwrap in two major stages, releasing nearly equal length of DNA in each stage. The first stage, attributed to the rupture of the outer turn is reversible, occurs at low forces (≈ (3 - 5) pNs) whereas in the second stage the inner turn ruptures irreversibly at high forces (between ≈ (9 - 15) or higher) pNs. We show that Brownian dynamics simulations using the Self-Organized Polymer model of the nucleosome capture the experimental findings, thus permitting us to discern the molecular details of the structural changes not only in DNA but also in the Histone Protein Core (HPC). Upon unwrapping of the outer turn, which is independent of the pulling direction, there is a transition from 1.6 turns to 1.0 turn DNA wound around the HPC. In contrast, the rupture of the inner turn, leading to less than 0.5 turn DNA around the HPC, depends on the pulling direction, and is controlled by energetic and kinetic barriers. The latter arises because the mechanical force has to produce sufficient torque to rotate (in an almost directed manner) the HPC by 180°. In contrast, during the rewrapping process, HPC rotation is stochastic, with the quenched force f_Q playing no role. Interestingly, if f_Q = 0 the HPC rotation is not required for rewrapping because the DNA ends are unconstrained. The assembly of the outer wrap upon force quench, as assessed by the decrease in the end-to-end distance (R_ee) of the DNA, nearly coincides with the increase in R_ee as force is increased, confirming the reversible nature of the 1.6 turns to 1.0 turn transition. The asymmetry in HPC rotation during unwrapping and rewrapping accounts for the observed hysteresis in the stretch-release cycles in single molecule pulling experiments. Experiments that could validate the prediction that HPC rotation, which gives rise to the kinetic barrier in the unwrapping process, are proposed.

中文翻译：

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核小体中强迫解开和力淬灭的组蛋白旋转的不对称性

核小体也是染色体的组成部分，也是转录调节因子。单分子拉动实验表明，核小体在两个主要阶段解缠，在每个阶段释放几乎等长的DNA。第一阶段归因于外圈的破裂是可逆的，发生在较小的力（≈（3-5）pNs）处，而第二阶段中的内圈在高的力下不可逆地破裂（在≈（9-15）之间或更高）。我们表明，使用核小体的自组织聚合物模型进行的布朗动力学模拟捕获了实验结果，从而使我们能够辨别不仅在DNA中而且在组蛋白核心（HPC）中结构变化的分子细节。展开与转向方向无关的外部匝时，从1.6匝过渡到1。DNA绕HPC绕0转。相反，内圈的破裂会导致HPC周围的DNA少于0.5圈，取决于拉动方向，并受到能量和动力学屏障的控制。后者的出现是因为机械力必须产生足够的扭矩以使HPC（以几乎定向的方式）旋转180°。相反，在重新包装过程中，HPC旋转是随机的，并具有淬灭力f _Q不起作用。有趣的是，如果f _Q = 0，则重新包装不需要HPC旋转，因为DNA末端不受限制。根据DNA的端对端距离（R _ee）的减少评估，在外加力淬灭后，外包装的组装几乎与R _ee的增加一致随着力的增加，确认了1.6圈到1.0圈过渡的可逆性。在展开和重新包裹过程中，HPC旋转的不对称性说明了单分子拉动实验中拉伸释放循环中观察到的滞后现象。提出了可以验证HPC旋转的预测的实验，该旋转会在展开过程中引起动力学障碍。