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通过冷冻聚焦离子束和冷冻电子断层扫描技术解析细胞内染色质结构

In-cell chromatin structure by Cryo-FIB and Cryo-ET.

作者信息

Hou Zhen, Zhang Peijun

机构信息

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK.

Division of Structural Biology, Nuffield Department of Medicine, University of Oxford, Oxford, OX3 7BN, UK; Diamond Light Source, Harwell Science and Innovation Campus, Didcot, OX11 0DE, UK.

出版信息

Curr Opin Struct Biol. 2025 Jun;92:103060. doi: 10.1016/j.sbi.2025.103060. Epub 2025 May 10.

Abstract

Chromatin, the complex of DNA and proteins that organises genetic material in eukaryotic cells, has been a focal point of biological research for over a century. Its structure determines critical functions such as gene regulation, DNA replication and chromosome segregation. Early models of chromatin were limited by technological constraints, but advancements in imaging, particularly X-ray and electron microscopy (EM), gradually unveiled its hierarchical organisation. The recent emergence of cryo-electron tomography (cryo-ET) coupled with cryo-focused ion beam (cryo-FIB) milling has revolutionised our understanding of chromatin organisation by providing native, three-dimensional (3D) views of various macromolecules and architectures of chromatin at unprecedented resolution. This review traces the historical progression of chromatin structural studies, from early EM and fluorescence microscopy to the transformative insights offered by cryo-ET, culminating in a synthesis of current knowledge and future directions.

摘要

染色质是真核细胞中组织遗传物质的DNA和蛋白质复合物,在一个多世纪以来一直是生物学研究的焦点。其结构决定了基因调控、DNA复制和染色体分离等关键功能。早期的染色质模型受到技术限制,但成像技术的进步,特别是X射线和电子显微镜(EM),逐渐揭示了其层次结构。最近,冷冻电子断层扫描(cryo-ET)与冷冻聚焦离子束(cryo-FIB)铣削技术的出现,以前所未有的分辨率提供了染色质各种大分子和结构的天然三维(3D)视图,彻底改变了我们对染色质组织的理解。本综述追溯了染色质结构研究的历史进程,从早期的电子显微镜和荧光显微镜到冷冻电子断层扫描提供的变革性见解,最终综合了当前的知识和未来的方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cd4/12371347/a689f2d01b2e/nihms-2105405-f0001.jpg

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