Genomic DNA in eukaryotes is organized into chromatin through association with core histone proteins to form nucleosomes. To understand the structure and function of chromatin, we must determine the structures of nucleosomes containing native DNA sequences. However, to date, our knowledge of nucleosome structures is mainly based on the crystallographic studies of the nucleosomes containing non-native DNA sequences. Here, we discuss the technical issues related to the determination of the nucleosome structures and review the few structural studies on native-like nucleosomes. We show how an antibody fragment-aided single-particle cryo-EM can be a useful method to determine the structures of nucleosomes containing genomic DNA. Finally, we provide a perspective for future structural studies of some native-like nucleosomes that play critical roles in chromatin functions.

真核生物中的基因组 DNA 通过与核心组蛋白结合形成核小体而组织成染色质。要了解染色质的结构和功能，我们必须确定含有天然 DNA 序列的核小体的结构。然而，迄今为止，我们对核小体结构的了解主要基于对含有非天然 DNA 序列的核小体的晶体学研究。在这里，我们讨论了与确定核小体结构相关的技术问题，并回顾了一些关于类天然核小体的结构研究。我们展示了抗体片段辅助的单粒子冷冻电镜如何成为确定含有基因组 DNA 的核小体结构的有用方法。最后，