Nucleosomes, the basic units of chromatin, package and regulate expression of eukaryotic genomes. Although the structure of the intact nucleosome is well characterized, little is known about structures of partially unwrapped, transient intermediates. In this study, we present nine cryo-EM structures of distinct conformations of nucleosome and subnucleosome particles. These structures show that initial DNA breathing induces conformational changes in the histone octamer, particularly in histone H3, that propagate through the nucleosome and prevent symmetrical DNA opening. Rearrangements in the H2A–H2B dimer strengthen interaction with the unwrapping DNA and promote nucleosome stability. In agreement with this, cross-linked H2A–H2B that cannot accommodate unwrapping of the DNA is not stably maintained in the nucleosome. H2A–H2B release and DNA unwrapping occur simultaneously, indicating that DNA is essential in stabilizing the dimer in the nucleosome. Our structures reveal intrinsic nucleosomal plasticity that is required for nucleosome stability and might be exploited by extrinsic protein factors.

中文翻译：

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组蛋白八聚体重新排列以适应 DNA 展开

核小体是染色质的基本单位，负责包装和调节真核基因组的表达。尽管完整核小体的结构已得到很好的表征，但对部分展开的瞬时中间体的结构知之甚少。在这项研究中，我们提出了九种不同构象的核小体和亚核小体颗粒的冷冻电镜结构。这些结构表明，最初的 DNA 呼吸会引起组蛋白八聚体的构象变化，特别是组蛋白 H3 中的变化，这些变化会通过核小体传播并阻止对称的 DNA 开放。H2A-H2B 二聚体中的重排加强了与展开的 DNA 的相互作用并促进核小体的稳定性。与此一致的是，不能适应 DNA 解包的交联 H2A-H2B 在核小体中不能稳定维持。H2A-H2B 释放和 DNA 解包同时发生，表明 DNA 对于稳定核小体中的二聚体至关重要。我们的结构揭示了核小体稳定性所需的内在核小体可塑性，并且可能被外在蛋白质因子利用。