DNA Sequence-Directed Organization of Chromatin: Structure-Based Computational Analysis of Nucleosome-Binding Sequences
DNA Sequence-Directed Organization of Chromatin: Structure-Based Computational Analysis of Nucleosome-Binding Sequences
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DOI：
10.1016/j.bpj.2008.11.040
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发表时间：
2009-03-18
影响因子：
3.4
通讯作者：
Olson, Wilma K.
中科院分区：
文献类型：
--
作者：
Balasubramanian, Sreekala;Xu, Fei;Olson, Wilma K.
DNA在核小体核心粒子上的折叠支配着真核生物分子生物学中的许多基本问题。在这项研究中，一组更新的序列依赖的经验“能量”函数，从其他蛋白质结合的DNA分子的结构，被用来研究核小体DNA的结构在多大程度上是由其潜在的序列决定的。这些电位用于估计沿各种左旋超螺旋途径在核小体中结合或抵抗摄取的一系列序列变形的成本，并推断导致特定结构形式的序列特征。变形分数反映了模板的选择，核小体结合DNA的每一步结构参数与其内在值的偏差，以及给定二聚体的序列依赖性“可变形性”。计算得分和结合倾向之间的对应关系指出了DNA序列和核小体折叠之间的微妙相互作用，例如，具有周期性间隔嘧啶嘌呤步骤的序列沿着弯曲模板以低成本变形，而抵抗变形的序列则倾向于更平滑的空间路径。然而，要成功预测一些分辨率最高的核小体定位序列的已知设置，需要一个具有“扭结和滑动”步骤的模板，就像在高分辨率核小体结构中发现的那样。
The folding of DNA on the nucleosome core particle governs many fundamental issues in eukaryotic molecular biology. In this study, an updated set of sequence-dependent empirical "energy" functions, derived from the structures of other protein-bound DNA molecules, is used to investigate the extent to which the architecture of nucleosomal DNA is dictated by its underlying sequence. The potentials are used to estimate the cost of deforming a collection of sequences known to bind or resist uptake in nucleosomes along various left-handed superhelical pathways and to deduce the features of sequence contributing to a particular structural form. The deformation scores reflect the choice of template, the deviations of structural parameters at each step of the nucleosome-bound DNA from their intrinsic values, and the sequence-dependent "deformability" of a given dimer. The correspondence between the computed scores and binding propensities points to a subtle interplay between DNA sequence and nucleosomal folding, e.g., sequences with periodically spaced pyrimidine-purine steps deform at low cost along a kinked template whereas sequences that resist deformation prefer a smoother spatial pathway. Successful prediction of the known settings of some of the best-resolved nucleosome-positioning sequences, however, requires a template with "kink-and-slide" steps like those found in high-resolution nucleosome structures.