Archaeal chromatin 'slinkies' are inherently dynamic complexes with deflected DNA wrapping pathways.
Archaeal chromatin 'slinkies' are inherently dynamic complexes with deflected DNA wrapping pathways.
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DOI：
10.7554/elife.65587
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发表时间：
2021-03-02
期刊：
影响因子：
7.7
通讯作者：
Luger K
中科院分区：
文献类型：
--
作者：
Bowerman S;Wereszczynski J;Luger K
真核生物和许多古细菌用组蛋白包装它们的DNA。当四种真核组蛋白将~147个DNA碱基对包裹到核小体中时，古细菌组蛋白形成“核小体样”复合物，其连续缠绕在60至500个DNA碱基对之间（“古小体”），这由晶体接触和细胞染色质分析表明。大型古生物体（>90个DNA碱基对）的溶液结构从未被直接观察到。在这里，我们利用分子动力学模拟，分析超离心，和cryoEM的结构特征的解决方案状态的古DNA较长。模拟揭示了动态增加的可访问性，而不中断的DNA结合或四聚化接口。Mg 2+浓度影响压实，cryoEM密度说明DNA被包裹在连续的子状态中，彼此呈90 °平面外排列。如果没有ATP依赖的重塑，古细菌可能会利用这些固有的动态平衡染色质包装和可及性。所有的动物、植物和真菌都属于一组被称为真核生物的生物体。另外两组是细菌和古生菌，包括单细胞的微生物。这三个群体都有基因，这些基因通常储存在长链DNA上。真核生物有如此多的DNA，它们使用称为组蛋白的蛋白质来帮助包装和组织每个细胞内的DNA。古生物也有简化的组蛋白，帮助储存它们的DNA，研究这些蛋白质可以揭示真核生物组蛋白最初是如何进化的。在真核生物中，八组组蛋白形成一个短圆柱体，将一小部分DNA组织成一种称为核小体的结构。每个细胞需要成千上万的核小体来排列它的DNA。真核细胞还含有其他蛋白质，这些蛋白质可以从组蛋白中释放出DNA片段，从而可以使用它们的遗传信息。这些组蛋白并不形成离散的核小体，相反，它们将DNA卷曲成“slinky样”的形状。目前还不清楚古细菌中的DNA包装是如何工作的，以及它与真核生物有何不同。Bowerman，Wereszczynski和Luger使用计算机模拟，生物化学和冷冻电子显微镜来研究古细菌的组蛋白。古细菌的“slinky样”组蛋白结构比核小体更灵活，可以像蛤壳一样打开和关闭。这种灵活性使得古细菌基因组中的信息很容易获得，因此，与真核生物不同，古细菌细胞可能不需要其他蛋白质来从组蛋白中释放DNA。包装DNA的能力使细胞能够包含更多的基因，因此进化组蛋白是真核生物进化的重要一步，包括动物的出现。细胞膜组蛋白可能反映了真核生物中组蛋白的早期版本，并可用于了解DNA包装是如何进化的。此外，更好地了解珊瑚虫可能有助于更好地解释它们在健康和全球生态系统中的作用，并使其能够用于工业应用。
Eukaryotes and many archaea package their DNA with histones. While the four eukaryotic histones wrap ~147 DNA base pairs into nucleosomes, archaeal histones form ‘nucleosome-like’ complexes that continuously wind between 60 and 500 base pairs of DNA (‘archaeasomes’), suggested by crystal contacts and analysis of cellular chromatin. Solution structures of large archaeasomes (>90 DNA base pairs) have never been directly observed. Here, we utilize molecular dynamics simulations, analytical ultracentrifugation, and cryoEM to structurally characterize the solution state of archaeasomes on longer DNA. Simulations reveal dynamics of increased accessibility without disruption of DNA-binding or tetramerization interfaces. Mg2+ concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90o out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility. All animals, plants and fungi belong to a group of living organisms called eukaryotes. The two other groups are bacteria and archaea, which include unicellular, microscopic organisms. All three groups have genes, which are typically stored on long strands of DNA. Eukaryotes have so much DNA that they use proteins called histones to help package and organize it inside each cell. Archaea also have simplified histones that help store their DNA, and studying these proteins could reveal how eukaryotic histones first evolved. In eukaryotes, groups of eight histones form a short cylinder that organizes a small section of DNA into a structure called a nucleosome. Each cell needs hundreds of thousands of nucleosomes to arrange its DNA. Eukaryotic cells also contain other proteins that release pieces of DNA from histones so that their genetic information can be used. The histones in Archaea don’t form discrete nucleosomes, instead, they coil DNA into ‘slinky-like’ shapes. It’s still unclear how DNA packing in archaea works and how it differs from eukaryotes. Bowerman, Wereszczynski and Luger used computer simulations, biochemistry and cryo-electron microscopy to study the histones from archaea. The archaeal ‘slinky-like’ histone structures are more flexible than nucleosomes, and can open and close like clamshells. This flexibility allows the information in the genomes of Archaea to be easily accessed, so, unlike in eukaryotes, archaeal cells may not need other proteins to release the DNA from the histones. The ability to package DNA allows cells to contain many more genes, so evolving histones was a vital step in the evolution of eukaryotic life, including the appearance of animals. Archaeal histones may reflect early versions of histones in eukaryotes, and can be used to understand how DNA packing has evolved. Furthermore, a greater understanding of Archaea may help better explain their role in health and global ecosystems, and allow their use in industrial applications.