DNA topology in chromatin is defined by nucleosome spacing.
DNA topology in chromatin is defined by nucleosome spacing.
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DOI：
10.1126/sciadv.1700957
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发表时间：
2017-10
期刊：
影响因子：
13.6
通讯作者：
Zhurkin VB
中科院分区：
文献类型：
--
作者：
Nikitina T;Norouzi D;Grigoryev SA;Zhurkin VB
核小体间距的变化导致染色质的拓扑多态性，从而影响DNA超螺旋和转录。在真核生物核小体中，DNA围绕组蛋白八聚体形成约1.7个超螺旋转角。然而，在通过X射线晶体学确定的核小体核心结构和圆形微型染色体中DNA拓扑结构的测量之间存在长期的差异，表明每个核小体只有~1.0个超螺旋圈。虽然提出了几个理论假设来解释这一矛盾的构象变异的核小体连接，没有实验测试。我们用精确定位的核小体分析了环形核小体阵列中DNA的拓扑性质。使用拓扑电泳分析和电子显微镜，我们证明了每个核小体的DNA连接数强烈依赖于核小体间距，从-1.4到-0.9不等。对于在天然染色质中发现的占主导地位的{10 n + 5}类核小体重复序列，我们的结果与先前观察到的DNA拓扑结构一致。因此，我们调和核小体阵列的核小体核心结构的拓扑性质，并提供了一个简单的解释天然染色质中的DNA拓扑结构与可变的DNA接头长度。本文描述的染色质纤维的拓扑多态性可能反映了含有活性或抑制基因的染色体结构域获得不同核小体间距以保留拓扑上不同的高级结构的更普遍趋势。
Nucleosome spacing variations cause topological polymorphism of chromatin that can affect DNA supercoiling and transcription. In eukaryotic nucleosomes, DNA makes ~1.7 superhelical turns around histone octamer. However, there is a long-standing discrepancy between the nucleosome core structure determined by x-ray crystallography and measurements of DNA topology in circular minichromosomes, indicating that there is only ~1.0 superhelical turn per nucleosome. Although several theoretical assumptions were put forward to explain this paradox by conformational variability of the nucleosome linker, none was tested experimentally. We analyzed topological properties of DNA in circular nucleosome arrays with precisely positioned nucleosomes. Using topological electrophoretic assays and electron microscopy, we demonstrate that the DNA linking number per nucleosome strongly depends on the nucleosome spacing and varies from −1.4 to −0.9. For the predominant {10n + 5} class of nucleosome repeats found in native chromatin, our results are consistent with the DNA topology observed earlier. Thus, we reconcile the topological properties of nucleosome arrays with nucleosome core structure and provide a simple explanation for the DNA topology in native chromatin with variable DNA linker length. Topological polymorphism of the chromatin fibers described here may reflect a more general tendency of chromosomal domains containing active or repressed genes to acquire different nucleosome spacing to retain topologically distinct higher-order structures.
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影响因子：
16.8
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发表时间：
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影响因子：
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