Department of Biochemistry and Howard Hughes Medical Institute, University of Colorado Boulder, Boulder, United States.
Department of Physics and Center for the Molecular Study of Condensed Soft Matter, Illinois Institute of Technology, Chicago, United States.
Elife. 2021 Mar 2;10:e65587. doi: 10.7554/eLife.65587.
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. Mg concentration influences compaction, and cryoEM densities illustrate that DNA is wrapped in consecutive substates arranged 90 out-of-plane with one another. Without ATP-dependent remodelers, archaea may leverage these inherent dynamics to balance chromatin packing and accessibility.
真核生物和许多古菌用组蛋白将其 DNA 包装。虽然四种真核生物组蛋白将约 147 个 DNA 碱基对包裹成核小体，但古菌组蛋白形成“类核小体”复合物，在 DNA 之间连续缠绕 60 到 500 个碱基对（“古菌核小体”），这是晶体接触和细胞染色质分析所表明的。从未直接观察到大于 90 个 DNA 碱基对的大型古菌核小体的溶液结构。在这里，我们利用分子动力学模拟、分析超速离心和 cryoEM 来对较长 DNA 上的古菌核小体在溶液状态下的结构进行特征描述。模拟显示了增加可及性的动力学，而不会破坏 DNA 结合或四聚体化界面。镁浓度会影响紧凑度，cryoEM 密度表明 DNA 以彼此之间成 90 度的连续亚状态缠绕。在没有 ATP 依赖性重塑酶的情况下，古菌可能会利用这些固有动力学来平衡染色质包装和可及性。
