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三维基因组视角下的细胞命运决定、器官再生和疾病。

3D genome perspective on cell fate determination, organ regeneration, and diseases.

机构信息

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.

出版信息

Cell Prolif. 2023 May;56(5):e13482. doi: 10.1111/cpr.13482. Epub 2023 May 17.

DOI:10.1111/cpr.13482
PMID:37199020
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10212718/
Abstract

The nucleosome is the fundamental subunit of chromatin. Nucleosome structures are formed by the combination of histone octamers and genomic DNA. Through a systematic and precise process of folding and compression, these structures form a 30-nm chromatin fibre that is further organized within the nucleus in a hierarchical manner, known as the 3D genome. Understanding the intricacies of chromatin structure and the regulatory mode governing chromatin interactions is essential for unravelling the complexities of cellular architecture and function, particularly in relation to cell fate determination, regeneration, and the development of diseases. Here, we provide a general overview of the hierarchical structure of chromatin as well as of the evolution of chromatin conformation capture techniques. We also discuss the dynamic regulatory changes in higher-order chromatin structure that occur during stem cell lineage differentiation and somatic cell reprogramming, potential regulatory insights at the chromatin level in organ regeneration, and aberrant chromatin regulation in diseases.

摘要

核小体是染色质的基本亚基。核小体结构由组蛋白八聚体和基因组 DNA 组成。通过一个系统和精确的折叠和压缩过程,这些结构形成了一个 30nm 的染色质纤维,然后在细胞核内以层次化的方式进一步组织,被称为三维基因组。了解染色质结构的复杂性和调控染色质相互作用的模式对于揭示细胞结构和功能的复杂性至关重要,特别是在细胞命运决定、再生和疾病发展方面。在这里,我们提供了染色质的层次结构以及染色质构象捕获技术的演变的概述。我们还讨论了在干细胞谱系分化和体细胞重编程过程中发生的高级染色质结构的动态调控变化、器官再生中染色质水平的潜在调控见解,以及疾病中异常的染色质调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/e31836f3d1d8/CPR-56-e13482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/800129d18b1b/CPR-56-e13482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/0a1d67b85363/CPR-56-e13482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/0ee106665a4a/CPR-56-e13482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/e31836f3d1d8/CPR-56-e13482-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/800129d18b1b/CPR-56-e13482-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/0a1d67b85363/CPR-56-e13482-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/0ee106665a4a/CPR-56-e13482-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7880/10212718/e31836f3d1d8/CPR-56-e13482-g005.jpg

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Nat Commun. 2023 Jan 13;14(1):213. doi: 10.1038/s41467-023-35879-5.
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An enhancer-based gene-therapy strategy for spatiotemporal control of cargoes during tissue repair.基于增强子的基因治疗策略,用于在组织修复过程中对货物进行时空控制。
Cell Stem Cell. 2023 Jan 5;30(1):96-111.e6. doi: 10.1016/j.stem.2022.11.012. Epub 2022 Dec 13.
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Structural variants drive context-dependent oncogene activation in cancer.
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Nature. 2022 Dec;612(7940):564-572. doi: 10.1038/s41586-022-05504-4. Epub 2022 Dec 7.
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Nat Genet. 2022 Dec;54(12):1919-1932. doi: 10.1038/s41588-022-01223-8. Epub 2022 Dec 5.
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