Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells
Condensed Chromatin Behaves like a Solid on the Mesoscale In Vitro and in Living Cells
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DOI：
10.1101/2020.05.06.079905
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发表时间：
2020-05
期刊：
影响因子：
64.5
通讯作者：
H. Strickfaden;Thomas O. Tolsma;A. Sharma;D. Underhill;J. Hansen;Michael J Hendzel;Michael J Hendzel-
中科院分区：
文献类型：
--
作者：
H. Strickfaden;Thomas O. Tolsma;A. Sharma;D. Underhill;J. Hansen;Michael J Hendzel;Michael J Hendzel-
核 DNA 与组蛋白结合形成染色质对于真核基因组的时间和空间控制至关重要。在这项研究中，我们检查了染色质在体外和体内的物理状态。我们的体外研究表明，天然染色质片段或重构核小体阵列的 MgCl2 依赖性自缔合产生了超分子缩合物，其成分受到物理约束且呈固体状。液体染色质浓缩物可以在体外产生，但只能使用非生理条件。通过测量活细胞中异染色质和常染色质内的 DNA 迁移率，我们发现染色质在体内也表现出类似固体的行为。然而，代表性的异染色质蛋白表现出类似液体的行为，并在固体染色质支架周围聚结。值得注意的是，即使透射电子显微镜显示染色质纤维之间的相互作用有限，常染色质和异染色质也表现出类似固体的行为。因此，我们的结果表明，染色质不是液体，而是以类似固体的材料状态存在，其特性通过纤维与纤维的相互作用来调节。
The association of nuclear DNA with histones to form chromatin is essential to the temporal and spatial control of eukaryotic genomes. In this study, we examined the physical state of chromatin in vitro and in vivo. Our in vitro studies demonstrate that MgCl2-dependent self-association of native chromatin fragments or reconstituted nucleosomal arrays produced supramolecular condensates whose constituents are physically constrained and solid-like. Liquid chromatin condensates could be generated in vitro, but only using non-physiological conditions. By measuring DNA mobility within heterochromatin and euchromatin in living cells, we show that chromatin also exhibits solid-like behavior in vivo. Representative heterochromatin proteins, however, displayed liquid-like behavior and coalesced around a solid chromatin scaffold. Remarkably, both euchromatin and heterochromatin showed solid-like behavior even when transmission electron microscopy revealed limited interactions between chromatin fibers. Our results therefore argue that chromatin is not liquid but exists in a solid-like material state whose properties are tuned by fiber-fiber interactions.