A novel roll-and-slide mechanism of DNA folding in chromatin: Implications for nucleosome positioning
A novel roll-and-slide mechanism of DNA folding in chromatin: Implications for nucleosome positioning
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DOI：
10.1016/j.jmb.2007.05.048
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发表时间：
2007-08-17
影响因子：
5.6
通讯作者：
Zhurkin, Victor B.
中科院分区：
文献类型：
--
作者：
Tolstorukov, Michael Y.;Colasanti, Andrew V.;Zhurkin, Victor B.
真核基因组如何编码DNA折叠成核小体，以及染色质的这种内在组织如何引导生物功能是人们广泛感兴趣的问题。核小体定位的物理基础在于DNA的序列依赖倾向于采用组蛋白结合所施加的紧密弯曲构型。传统上只考虑DNA的弯曲和扭转变形，而忽略了相邻碱基对的横向位移的影响。然而，我们证明，这些位移具有比想象中更重要的结构性作用。具体地说，在DNA的局部各向异性弯曲部位观察到的横向滑动变形定义了它在染色质中的超螺旋轨迹。此外，在核小体上变形DNA的计算成本是特定于序列的：在最佳位置的序列中，最容易变形的碱基对步骤(CA：TG和TA)发生在大的正滑动和负滚动位置(DNA弯曲到小凹槽中)。这些结论建立在对DNA的处理上，它超越了传统的带状模型，在估计DNA变形能时纳入了“真实”双链的所有基本自由度。事实上，只有在考虑了侧向滑动位移之后，我们才能解释在核小体结构中发现的DNA的序列特异性折叠。预测的核小体位置和观察到的核小体位置之间的密切对应表明了我们的“结构”方法在核小体定位的计算机绘图中的潜在优势。(C)2007爱思唯尔有限公司。保留所有权利。
How eukaryotic genomes encode the folding of DNA into nucleosomes and how this intrinsic organization of chromatin guides biological function are questions of wide interest. The physical basis of nucleosome positioning lies in the sequence-dependent propensity of DNA to adopt the tightly bent configuration imposed by the binding of the histone proteins. Traditionally, only DNA bending and twisting deformations are considered, while the effects of the lateral displacements of adjacent base pairs are neglected. We demonstrate, however, that these displacements have a much more important structural role than ever imagined. Specifically, the lateral Slide deformations observed at sites of local anisotropic bending of DNA define its superhelical trajectory in chromatin. Furthermore, the computed cost of deforming DNA on the nucleosome is sequence-specific: in optimally positioned sequences the most easily deformed base-pair steps (CA:TG and TA) occur at sites of large positive Slide and negative Roll (where the DNA bends into the minor groove). These conclusions rest upon a treatment of DNA that goes beyond the conventional ribbon model, incorporating all essential degrees of freedom of "real" duplexes in the estimation of DNA deformation energies. Indeed, only after lateral Slide displacements are considered are we able to account for the sequence-specific folding of DNA found in nucleosome structures. The close correspondence between the predicted and observed nucleosome locations demonstrates the potential advantage of our "structural" approach in the computer mapping of nucleosome positioning. (c) 2007 Elsevier Ltd. All rights reserved.