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细胞衰老过程中染色质分布失衡决定了旁斑动态变化。

Imbalanced chromatin distribution in cellular senescence specifies paraspeckle dynamics.

作者信息

Lee Joonwoo, Choi Jinmi, Park Jeongeun, Lee Seonduk, Cho Eun-Jung, Gwon Youngdae

机构信息

Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, 16419, Republic of Korea.

Sungkyunkwan University School of Pharmacy, Suwon, 16419, Republic of Korea.

出版信息

Genome Biol. 2025 Sep 2;26(1):264. doi: 10.1186/s13059-025-03757-6.

DOI:10.1186/s13059-025-03757-6
PMID:40898359
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12406609/
Abstract

Cellular senescence is accompanied by extensive genomic reorganization, such as senescence-associated heterochromatin foci and expanded interchromatin compartments, to ultimately affect gene expression. Here, we demonstrate that chromatin structural changes in senescent cells drive significant alterations in the phase behavior and motility of paraspeckles, a type of interchromatin compartment condensate. We observe increased numbers, size, and elongation of paraspeckles harboring NONO and NEAT1_2, driven by elevated levels of those components, consistent with the micellization model of longitudinal growth rather than condensate coalescence. Enhanced paraspeckle motility is associated with HP1α-mediated heterochromatin condensation and interchromatin expansion found in cellular senescence.

摘要

细胞衰老伴随着广泛的基因组重组,如衰老相关异染色质聚集体和扩展的染色质间区室,最终影响基因表达。在此,我们证明衰老细胞中的染色质结构变化驱动了副斑点(一种染色质间区室凝聚物)的相行为和运动性的显著改变。我们观察到,含有NONO和NEAT1_2的副斑点数量增加、尺寸增大且伸长,这是由这些组分水平升高所驱动的,这与纵向生长的胶束化模型一致,而非凝聚物聚结。副斑点运动性增强与细胞衰老中HP1α介导的异染色质凝聚和染色质间扩展有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a4b/12406609/e65e8f1f2f5f/13059_2025_3757_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a4b/12406609/d9447f07014c/13059_2025_3757_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a4b/12406609/e65e8f1f2f5f/13059_2025_3757_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a4b/12406609/d9447f07014c/13059_2025_3757_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a4b/12406609/e65e8f1f2f5f/13059_2025_3757_Fig2_HTML.jpg

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本文引用的文献

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Condensate interfacial forces reposition DNA loci and probe chromatin viscoelasticity.凝聚相界面力重定位 DNA 位置并探测染色质粘弹性。
Cell. 2024 Sep 19;187(19):5282-5297.e20. doi: 10.1016/j.cell.2024.07.034. Epub 2024 Aug 20.
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Reduced dynamicity and increased high-order protein assemblies in dense fibrillar component of the nucleolus under cellular senescence.细胞衰老时核仁密集纤维成分中动态性降低和高级蛋白质组装增加。
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Detection of senescence using machine learning algorithms based on nuclear features.
基于核特征的机器学习算法检测衰老。
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HIRA vs. DAXX: the two axes shaping the histone H3.3 landscape.HIRA 与 DAXX:塑造组蛋白 H3.3 景观的两个轴。
Exp Mol Med. 2024 Feb;56(2):251-263. doi: 10.1038/s12276-023-01145-3. Epub 2024 Feb 1.
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PML modulates epigenetic composition of chromatin to regulate expression of pro-metastatic genes in triple-negative breast cancer.PML 通过调节染色质的表观遗传组成来调节三阴性乳腺癌中促转移基因的表达。
Nucleic Acids Res. 2023 Nov 10;51(20):11024-11039. doi: 10.1093/nar/gkad819.
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Redistribution of lamina-associated domains reshapes binding of pioneer factor FOXA2 in development of nonalcoholic fatty liver disease.层粘连相关结构域的再分布重塑了先驱因子 FOXA2 在非酒精性脂肪性肝病发生过程中的结合。
Genome Res. 2022 Nov-Dec;32(11-12):1981-1992. doi: 10.1101/gr.277149.122. Epub 2022 Dec 15.
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Epigenetic regulation of aging: implications for interventions of aging and diseases.衰老的表观遗传学调控:干预衰老和疾病的意义。
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Early SRC activation skews cell fate from apoptosis to senescence.早期 SRC 的激活会使细胞命运从凋亡转向衰老。
Sci Adv. 2022 Apr 8;8(14):eabm0756. doi: 10.1126/sciadv.abm0756.
10
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