通过抑制与衰老相关的先驱因子AP-1的作用,FOXM1表达可以逆转衰老的染色体配置
Fábio J Ferreira1,2,3,4, Mafalda Galhardo1,2,3, João M Nogueira1,2,5
1i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135, Porto, Portugal.
Nature communications
|March 26, 2025
概括
老龄化导致有害的基因表达变化. 这项研究揭示了FOXM1的存在.
科学领域:
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞衰老 细胞衰老
背景情况:
- 衰老会改变基因表达,导致有害的细胞表型,如衰老.
- 表观遗传变化驱动衰老基因的激活,但染色体可访问性变化不太清楚.
- 需要阐明自然衰老中与年龄相关的染色质重塑背后的机制.
研究的目的:
- 研究人类皮肤纤维细胞 (HDF) 中染色质可访问性的与年龄相关的变化.
- 确定与年轻和老年染色体相关的关键转录因子结合动机.
- 阐明FOXM1在与年龄相关的染色质重塑和衰老预防中的作用.
主要方法:
- 跨越广泛的年龄范围 (新生儿到八十多岁) 的HDF中染色质可访问性概况.
- 在特定年龄的可访问区域中对转录因子结合基因丰富的分析.
- 功能性研究涉及增强体删除和老化细胞中的异位FOXM1表达.
主要成果:
- 新生儿HDF显示TEAD结合基因的丰富,而老年HDF显示AP-1结合基因的丰富.
- 调节TEAD4和FOXM1的新型依赖年龄增强剂随着年龄的增长而失去可访问性,并在删除后驱动衰老.
- 在老年细胞中,子宫外FOXM1表达通过抑制AP-1复合体成员,部分恢复了年轻的染色质可访问性.
结论:
- 通过保持年轻的染色质可访问性,FOXM1在预防衰老方面发挥着至关重要的作用.
- 增强器可访问性和FOXM1功能与年龄相关的下降有助于衰老.
- 在染色体重塑过程中,FOXM1具有层次的作用,以抵消因年龄而导致的衰老.
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