与衰老相关的染色体重新连接促进炎症和可转移元素激活
Audrey Dalgarno1,2, Shane A Evans3, Maxfield M G Kelsey1,2
1Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, USA.
bioRxiv : the preprint server for biology
|July 16, 2025
概括
细胞衰老涉及3D基因组组织的变化,影响基因表达和炎症. 这项研究揭示了染色体结构如何驱动与衰老相关的分泌表型 (SASP) 和逆转移子激活.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞生物学 细胞生物学
背景情况:
- 细胞衰老是一种不可逆转的细胞循环停止状态,通过衰老相关的分泌表型 (SASP) 与衰老和疾病有关.
- 虽然已知转录和表观遗传因素是衰老的驱动因素,但更高阶基因组组织的作用不太了解.
研究的目的:
- 研究3D基因组架构对细胞衰老的贡献.
- 在增殖,静止和衰老的人类纤维细胞中分析高分辨率的染色质组织.
主要方法:
- 为不同细胞状态中的人类纤维细胞生成最高分辨率的Hi-C地图 (~3 kb).
- 对3D基因组架构的全面分析,包括隔间,子隔间和染色质循环.
- 结构变化与DNA甲基化,基因表达和逆转移素活性的相关性.
主要成果:
- 在衰老细胞中广泛改造染色体结构,并进行隔间切换和增加染色体循环.
- 改变的3D基因组结构与DNA低甲基化,SASP基因表达和LINE-1逆转移子的激活相关.
- 不同的染色体配置区分了老化和静止,尽管类似的基因抑制.
结论:
- 3D基因组架构在建立和维持衰老状态方面发挥着至关重要的作用.
- 染色质结构的变化促进SASP和炎症通路的表达.
- 静止细胞与衰老细胞共享炎症基因表达,突显了实验设计的重要性.
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