The importance of histone variant H2A.Z in transcription regulation has been well established, yet its mechanism-of-action remains enigmatic. Conflicting evidence exists in support of both an activating and a repressive role of H2A.Z in transcription. Here we report cryo-electron microscopy (cryo-EM) structures of nucleosomes and chromatin fibers containing H2A.Z and those containing canonical H2A. The structures show that H2A.Z incorporation results in substantial structural changes in both nucleosome and chromatin fiber. While H2A.Z increases the mobility of DNA terminus in nucleosomes, it simultaneously enables nucleosome arrays to form a more regular and condensed chromatin fiber. We also demonstrated that H2A.Z’s ability to enhance nucleosomal DNA mobility is largely attributed to its characteristic shorter C-terminus. Our study provides the structural basis for H2A.Z-mediated chromatin regulation, showing that the increase flexibility of the DNA termini in H2A.Z nucleosomes is central to its dual-functions in chromatin regulation and in transcription.

中文翻译：

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组蛋白变体 H2A.Z 调控染色质的结构基础

组蛋白变体 H2A.Z 在转录调控中的重要性已得到充分证实，但其作用机制仍然是个谜。存在相互矛盾的证据支持 H2A.Z 在转录中的激活和抑制作用。在这里，我们报告了含有 H2A.Z 和含有规范 H2A 的核小体和染色质纤维的低温电子显微镜 (cryo-EM) 结构。这些结构表明，H2A.Z 的掺入导致核小体和染色质纤维的显着结构变化。虽然 H2A.Z 增加了核小体中 DNA 末端的移动性，但它同时使核小体阵列能够形成更规则和更密集的染色质纤维。我们还证明了 H2A.Z 增强核小体 DNA 迁移率的能力很大程度上归因于其特征性的较短 C 末端。