Sub-nucleosomal Genome Structure Reveals Distinct Nucleosome Folding Motifs
Sub-nucleosomal Genome Structure Reveals Distinct Nucleosome Folding Motifs
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DOI：
10.1016/j.cell.2018.12.014
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发表时间：
2019-01-24
期刊：
影响因子：
64.5
通讯作者：
Taniguchi, Yuichi
中科院分区：
文献类型：
--
作者：
Ohno, Masae;Ando, Tadashi;Taniguchi, Yuichi
阐明控制全基因组层次染色质结构的全局和局部规则仍然是一个关键挑战。目前的高通量染色体构象捕获（Hi-C）技术已经确定了大规模的染色质结构基序，如拓扑相关的结构域和环。然而，在最小或核小体规模的结构规则仍然知之甚少。在这里，我们耦合核小体分辨Hi-C技术与模拟退火分子动力学（SA-MD）模拟，以揭示核小体的三维空间分布及其在染色质中的全基因组方向。我们的方法称为Hi-CO，揭示了酵母基因组中不同的核小体折叠基序。我们的研究结果揭示了两种类型的基本二级结构模体在核小体折叠：α-四面体和β-菱形类似于α螺旋和β折叠模体在蛋白质折叠。使用突变体和细胞周期同步的细胞，我们进一步揭示了特定的核小体定位和方向耦合到表观遗传特征在个别基因座的图案。通过阐明真核染色质分子水平的结构-功能关系，我们的研究结果建立了核小体折叠的组织原则。
Elucidating the global and local rules that govern genome-wide, hierarchical chromatin architecture remains a critical challenge. Current high-throughput chromosome conformation capture (Hi-C) technologies have identified large-scale chromatin structural motifs, such as topologically associating domains and looping. However, structural rules at the smallest or nucleosome scale remain poorly understood. Here, we coupled nucleosome-resolved Hi-C technology with simulated annealing-molecular dynamics (SA-MD) simulation to reveal 3D spatial distributions of nucleosomes and their genome-wide orientation in chromatin. Our method, called Hi-CO, revealed distinct nucleosome folding motifs across the yeast genome. Our results uncovered two types of basic secondary structural motifs in nucleosome folding: alpha-tetrahedron and beta-rhombus analogous to alpha helix and beta sheet motifs in protein folding. Using mutants and cell-cycle-synchronized cells, we further uncovered motifs with specific nucleosome positioning and orientation coupled to epigenetic features at individual loci. By illuminating molecular-level structure-function relationships in eukaryotic chromatin, our findings establish organizational principles of nucleosome folding.