Topological polymorphism of the two-start chromatin fiber.
Topological polymorphism of the two-start chromatin fiber.
复制标题
DOI：
10.1016/j.bpj.2015.04.015
复制
发表时间：
2015-05
影响因子：
3.4
通讯作者：
D. Norouzi;V. Zhurkin
中科院分区：
文献类型：
--
作者：
D. Norouzi;V. Zhurkin
有关 30 nm 纤维中核小体空间组织的具体细节仍然未知。为了研究这一点，我们分析了具有短 DNA 连接子 L = 13–37 bp（核小体重复长度 (NRL) = 160–184 bp）的双起始核小体纤维的所有立体化学可能构型。四个超螺旋参数——核小体的倾斜度、扭曲、上升和直径——独特地描述了规则的对称纤维。纤维的能量被定义为四项的总和：连接 DNA 的弹性能、空间排斥、静电以及两个堆叠核小体之间的现象学（H4 尾部酸性斑块）相互作用。通过根据超螺旋参数优化纤维能量，我们发现纤维中存在两种类型的拓扑转变（与倾斜角的变化相关）：一种是由接头 DNA 扭曲的突然 360° 变化引起的（DNA 连接数的变化，ΔLk= 1），另一种是由接头的过度交叉引起的（ΔLk= 2）。据我们所知，早期发布的计算中并未报道双起始光纤的这种拓扑多态性。重要的是，具有接头 L = 10n 和 10n+ 5 bp 的纤维的最佳配置的特点是 DNA 连接数的不同值，也就是说，它们在拓扑上是不同的。我们的结果与实验观察结果一致，例如60°至70°的倾角（核小体盘与纤维轴之间的角度）、螺旋上升、直径和纤维的左旋性。此外，我们还做出了一些可测试的预测，其中包括 L = 10n 和 10n+ 5 bp 的纤维中不同程度的 DNA 超螺旋、两种类型纤维的不同灵活性，以及局部 NRL 与酵母基因组不同部分的转录水平之间的相关性。
Specific details concerning the spatial organization of nucleosomes in 30 nm fibers remain unknown. To investigate this, we analyzed all stereochemically possible configurations of two-start nucleosome fibers with short DNA linkers L = 13–37 bp (nucleosome repeat length (NRL) = 160–184 bp). Four superhelical parameters—inclination of nucleosomes, twist, rise, and diameter—uniquely describe a regular symmetric fiber. The energy of a fiber is defined as the sum of four terms: elastic energy of the linker DNA, steric repulsion, electrostatics, and a phenomenological (H4 tail–acidic patch) interaction between two stacked nucleosomes. By optimizing the fiber energy with respect to the superhelical parameters, we found two types of topological transition in fibers (associated with the change in inclination angle): one caused by an abrupt 360° change in the linker DNA twisting (change in the DNA linking number,ΔLk= 1), and another caused by overcrossing of the linkers (ΔLk= 2). To the best of our knowledge, this topological polymorphism of the two-start fibers was not reported in the computations published earlier. Importantly, the optimal configurations of the fibers with linkers L = 10nand 10n+ 5 bp are characterized by different values of the DNA linking number—that is, they are topologically different. Our results are consistent with experimental observations, such as the inclination 60° to 70° (the angle between the nucleosomal disks and the fiber axis), helical rise, diameter, and left-handedness of the fibers. In addition, we make several testable predictions, among them different degrees of DNA supercoiling in fibers with L = 10nand 10n+ 5 bp, different flexibility of the two types of fibers, and a correlation between the local NRL and the level of transcription in different parts of the yeast genome.