Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Diamond Light Source, Harwell Science and Innovation Campus, Didcot, UK.
Nat Commun. 2023 Oct 10;14(1):6324. doi: 10.1038/s41467-023-42072-1.
The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.
染色质的结构在调节基因转录、DNA 复制和修复以及染色体分离中起着关键作用。然而，这种结构仍然难以捉摸。在这里，我们使用冷冻断裂纤维和冷冻电子断层扫描技术，描绘了完整的人 T 淋巴细胞间期天然染色质纤维的 3D 结构，并确定了不同构象核小体的原位结构。这些染色质纤维不是作为均匀的 30nm 单链或双链纤维结构，而是由核小体的松弛、可变的之字形排列组成，通过直的连接 DNA 连接。带有少量 H1 和连接 DNA 密度的核小体随机分布，没有任何空间偏好。这项工作将激发未来在健康和疾病等许多不同细胞条件下，在单个核小体水平和群体水平上对原位天然染色质结构进行高分辨率研究。
