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近年来,染色体捕获技术的进步揭示了生殖细胞、健康和疾病中三维基因组结构。

Recent advances in chromosome capture techniques unraveling 3D genome architecture in germ cells, health, and disease.

机构信息

Laboratory of Animal Nutrition and Feed Science, Animal Science Department, Faculty of Animal and Agricultural Sciences, Universitas Diponegoro, Semarang, Indonesia.

Research Center for Animal Husbandry, National Research and Innovation Agency, Bogor, Indonesia.

出版信息

Funct Integr Genomics. 2023 Jun 29;23(3):214. doi: 10.1007/s10142-023-01146-5.

DOI:10.1007/s10142-023-01146-5
PMID:37386239
Abstract

In eukaryotes, the genome does not emerge in a specific shape but rather as a hierarchial bundle within the nucleus. This multifaceted genome organization consists of multiresolution cellular structures, such as chromosome territories, compartments, and topologically associating domains, which are frequently defined by architecture, design proteins including CTCF and cohesin, and chromatin loops. This review briefly discusses the advances in understanding the basic rules of control, chromatin folding, and functional areas in early embryogenesis. With the use of chromosome capture techniques, the latest advancements in technologies for visualizing chromatin interactions come close to revealing 3D genome formation frameworks with incredible detail throughout all genomic levels, including at single-cell resolution. The possibility of detecting variations in chromatin architecture might open up new opportunities for disease diagnosis and prevention, infertility treatments, therapeutic approaches, desired exploration, and many other application scenarios.

摘要

在真核生物中,基因组并非以特定的形状出现,而是在核内呈现出一种层次化的束状结构。这种多方面的基因组组织包括多分辨率的细胞结构,如染色体区域、隔室和拓扑关联域,它们通常由结构、设计蛋白(包括 CTCF 和黏连蛋白)和染色质环来定义。这篇综述简要讨论了在理解早期胚胎发生中控制、染色质折叠和功能区域的基本规则方面的进展。利用染色体捕获技术,可视化染色质相互作用的技术的最新进展几乎可以揭示出整个基因组水平(包括单细胞分辨率)的 3D 基因组形成框架,其细节令人难以置信。检测染色质结构变异的可能性可能为疾病诊断和预防、不孕治疗、治疗方法、期望的探索以及许多其他应用场景开辟新的机会。

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本文引用的文献

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Suppression of liquid-liquid phase separation by 1,6-hexanediol partially compromises the 3D genome organization in living cells.1,6-己二醇部分抑制液-液相分离会破坏活细胞中的三维基因组组织。
Nucleic Acids Res. 2021 Oct 11;49(18):10524-10541. doi: 10.1093/nar/gkab249.
2
A Structure-Based Mechanism for DNA Entry into the Cohesin Ring.一种基于结构的 DNA 进入黏连环的机制。
Mol Cell. 2020 Sep 17;79(6):917-933.e9. doi: 10.1016/j.molcel.2020.07.013. Epub 2020 Aug 4.
3
A WIZ/Cohesin/CTCF Complex Anchors DNA Loops to Define Gene Expression and Cell Identity.
一个 WIZ/黏合蛋白/CTCF 复合物将 DNA 环锚定到定义基因表达和细胞身份。
Cell Rep. 2020 Apr 14;31(2):107503. doi: 10.1016/j.celrep.2020.03.067.
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Redundant and specific roles of cohesin STAG subunits in chromatin looping and transcriptional control.黏连蛋白 STAG 亚基在染色质环化和转录调控中的冗余和特异作用。
Genome Res. 2020 Apr;30(4):515-527. doi: 10.1101/gr.253211.119. Epub 2020 Apr 6.
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Lamina-associated domains: peripheral matters and internal affairs.层粘连相关域:周边事务与内部事务。
Genome Biol. 2020 Apr 2;21(1):85. doi: 10.1186/s13059-020-02003-5.
6
Loss of an H3K9me anchor rescues laminopathy-linked changes in nuclear organization and muscle function in an Emery-Dreifuss muscular dystrophy model.缺失 H3K9me 锚定可挽救 Emery-Dreifuss 肌营养不良症模型中核组织和肌肉功能相关的核纤层蛋白病变化。
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