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Mechanical properties of symmetric and asymmetric DNA A-tracts: implications for looping and nucleosome positioning

机译:对称和不对称DNA A轴的机械特性:对环和核小体定位的影响

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摘要

A-tracts are functionally important DNA sequences which induce helix bending and have peculiar structural properties. While A-tract structure has been qualitatively well characterized, their mechanical properties remain controversial. A-tracts appear structurally rigid and resist nucleosome formation, but seem flexible in DNA looping. In this work, we investigate mechanical properties of symmetric AnTn and asymmetric A2n tracts for n = 3, 4, 5 using two types of coarse-grained models. The first model represents DNA as an ensemble of interacting rigid bases with non-local quadratic deformation energy, the second one treats DNA as an anisotropically bendable and twistable elastic rod. Parameters for both models are inferred from microsecond long, atomic-resolution molecular dynamics simulations. We find that asymmetric A-tracts are more rigid than the control G/C-rich sequence in localized distortions relevant for nucleosome formation, but are more flexible in global bending and twisting relevant for looping. The symmetric tracts, in contrast, are more rigid than asymmetric tracts and the control, both locally and globally. Our results can reconcile the contradictory stiffness data on A-tracts and suggest symmetric A-tracts to be more efficient in nucleosome exclusion than the asymmetric ones. This would open a new possibility of gene expression manipulation using A-tracts.
机译:A序列是功能上重要的DNA序列,可诱导螺旋弯曲并具有特殊的结构特性。尽管对A管道的结构进行了定性分析,但其机械性能仍存在争议。 A束在结构上似乎是刚性的,并能抵抗核小体的形成,但在DNA循环中似乎具有柔性。在这项工作中,我们使用两种粗粒度模型研究了n = 3、4、5时对称的AnTn和不对称的A2n区域的力学性能。第一个模型将DNA表示为相互作用的刚性碱基与非局部二次变形能的集合,第二个模型将DNA视为各向异性可弯曲且可扭曲的弹性杆。这两个模型的参数都是从微秒长的原子分辨率分子动力学模拟推论得出的。我们发现,不对称的A束在与核小体形成有关的局部畸变中比富含G / C的对照序列更坚硬,但在与弯曲相关的整体弯曲和扭曲方面更灵活。相反,在本地和全局上,对称区域比非对称区域和控制区域更加严格。我们的结果可以调和A轴上相互矛盾的刚度数据,并建议对称A轴比不对称A轴在核小体排斥方面更有效。这将开创使用A谱进行基因表达操纵的新可能性。

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