Gene Ceter, Department of Biochemistry, University of Munich LMU, 81377, Munich, Germany.
Cryo EM Facility, Max Planck Institute for Biochemistry, 82152, Martinsried, Germany.
Nat Commun. 2018 Apr 6;9(1):1330. doi: 10.1038/s41467-018-03677-z.
Nucleosomes, the basic unit of chromatin, package and regulate expression of eukaryotic genomes. Nucleosomes are highly dynamic and are remodeled with the help of ATP-dependent remodeling factors. Yet, the mechanism of DNA translocation around the histone octamer is poorly understood. In this study, we present several nucleosome structures showing histone proteins and DNA in different organizational states. We observe that the histone octamer undergoes conformational changes that distort the overall nucleosome structure. As such, rearrangements in the histone core α-helices and DNA induce strain that distorts and moves DNA at SHL 2. Distortion of the nucleosome structure detaches histone α-helices from the DNA, leading to their rearrangement and DNA translocation. Biochemical assays show that cross-linked histone octamers are immobilized on DNA, indicating that structural changes in the octamer move DNA. This intrinsic plasticity of the nucleosome is exploited by chromatin remodelers and might be used by other chromatin machineries.
核小体是染色质的基本单位，对真核基因组的包装和调控表达起作用。核小体具有高度的动态性，在 ATP 依赖的重塑因子的帮助下进行重塑。然而，DNA 围绕组蛋白八聚体的迁移机制仍不清楚。在这项研究中，我们呈现了几个核小体结构，展示了不同组织状态的组蛋白和 DNA。我们观察到组蛋白八聚体发生构象变化，扭曲了整个核小体结构。因此，组蛋白核心α-螺旋和 DNA 的重排会产生应变，使 DNA 在 SHL 2 处扭曲和移动。核小体结构的扭曲使组蛋白α-螺旋脱离 DNA，导致其重排和 DNA 易位。生化分析表明，交联的组蛋白八聚体固定在 DNA 上，这表明八聚体的结构变化会带动 DNA 运动。核小体的这种固有柔韧性被染色质重塑因子利用，也可能被其他染色质机器利用。
