Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription.
Topological diversity of chromatin fibers: Interplay between nucleosome repeat length, DNA linking number and the level of transcription.
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染色质纤维的拓扑多样性：核小体重复长度，DNA连接数量和转录水平之间的相互作用。
DOI：
10.3934/biophy.2015.4.613
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发表时间：
2015
期刊：
影响因子：
1.5
通讯作者：
Zhurkin VB
中科院分区：
文献类型：
--
作者：
Norouzi D;Katebi A;Cui F;Zhurkin VB
核小体在30纳米纤维中的空间组织仍然是未知的细节。为了解决这个问题，我们分析了具有DNA接头L = 10-70 bp（核小体重复长度NRL = 157-217 bp）的双起始染色质纤维的所有立体化学可能构型。在我们的模型中，纤维的能量是连接体DNA的弹性能、空间排斥、静电和两个堆叠的核小体之间的H4尾-酸性补丁相互作用的总和。我们发现了两个家庭的积极可行的构象的纤维-一个观察到较早，和其他小说。来自两个家族的纤维的特征在于不同的DNA连接数，也就是说，它们在拓扑结构上是不同的。值得注意的是，纤维的最佳几何形状及其拓扑结构取决于接头长度：接头L = 10 n和10 n + 5 bp的纤维每个核小体的DNA连接数ΔLk分别为−1.5和−1.0。换句话说，DNA超螺旋的水平与染色质纤维中核小体间接头的长度直接相关（因此与NRL直接相关）。我们推测，这种拓扑多态性的染色质纤维可能在转录过程中发挥作用，这是已知的RNA聚合酶上游和下游产生不同水平的DNA超螺旋。对活性和沉默酵母基因中NRL分布的全基因组分析得出的结果与这一假设一致。
The spatial organization of nucleosomes in 30-nm fibers remains unknown in detail. To tackle this problem, we analyzed all stereochemically possible configurations of two-start chromatin fibers with DNA linkers L = 10–70 bp (nucleosome repeat length NRL = 157–217 bp). In our model, the energy of a fiber is a sum of the elastic energy of the linker DNA, steric repulsion, electrostatics, and the H4 tail-acidic patch interaction between two stacked nucleosomes. We found two families of energetically feasible conformations of the fibers—one observed earlier, and the other novel. The fibers from the two families are characterized by different DNA linking numbers—that is, they are topologically different. Remarkably, the optimal geometry of a fiber and its topology depend on the linker length: the fibers with linkers L = 10n and 10n + 5 bp have DNA linking numbers per nucleosome ΔLk ≈ −1.5 and −1.0, respectively. In other words, the level of DNA supercoiling is directly related to the length of the inter-nucleosome linker in the chromatin fiber (and therefore, to NRL). We hypothesize that this topological polymorphism of chromatin fibers may play a role in the process of transcription, which is known to generate different levels of DNA supercoiling upstream and downstream from RNA polymerase. A genome-wide analysis of the NRL distribution in active and silent yeast genes yielded results consistent with this assumption.