Physical and data structure of 3D genome
Physical and data structure of 3D genome
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DOI：
10.1126/sciadv.aay4055
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发表时间：
2020-01-01
期刊：
影响因子：
13.6
通讯作者：
Szleifer, Igal
中科院分区：
文献类型：
--
作者：
Huang, Kai;Li, Yue;Szleifer, Igal
随着教科书上基于30纳米纤维的染色质折叠观点受到挑战，有人提出间期DNA具有不规则的10纳米核小体聚合物结构，其折叠原理尚不清楚。然而，实验进展表明，这种不规则堆积与许多重要的物理性质有关，从聚合物物理学的角度来看，这些物理性质令人费解。在这里，我们表明，要协调这些奇异的特性，就必须将三维基因组模块化为位于 DNA 双螺旋线性拓扑之上的树形数据结构，并与 DNA 双螺旋的线性拓扑形成鲜明对比。这些功能模块需要通过开放主干连接和隔离，从而以准自相似的方式产生多孔和异质堆积，正如我们的电子和光学成像所揭示的那样。我们的多尺度理论和实验结果表明，无序染色质纤维存在高阶通用折叠原理，以避免缠结并实现其生物学功能。
With the textbook view of chromatin folding based on the 30-nm fiber being challenged, it has been proposed that interphase DNA has an irregular 10-nm nucleosome polymer structure whose folding philosophy is unknown. Nevertheless, experimental advances suggest that this irregular packing is associated with many nontrivial physical properties that are puzzling from a polymer physics point of view. Here, we show that the reconciliation of these exotic properties necessitates modularizing three-dimensional genome into tree data structures on top of, and in striking contrast to, the linear topology of DNA double helix. These functional modules need to be connected and isolated by an open backbone that results in porous and heterogeneous packing in a quasi-self-similar manner, as revealed by our electron and optical imaging. Our multiscale theoretical and experimental results suggest the existence of higher-order universal folding principles for a disordered chromatin fiber to avoid entanglement and fulfill its biological functions.