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通过调解SUV39H1/H2降解,METTL3/METTL14保持人类细胞核的完整性
Yongli Shan1,2,3,4, Yanqi Zhang5,6,7, Yanxing Wei8
1Key Laboratory of Immune Response and Immunotherapy, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China. shan_yongli@gibh.ac.cn.
通过降解SUV39H1/H2蛋白质,METTL3/METTL14复合体维持了人类胚胎干细胞 (hESCs) 中的核细胞完整性和自我更新. 这阻止了H3K9me3的积累,保持了核细胞的结构和功能.
科学领域:
- 细胞生物学 细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 核对核糖体生物发生至关重要,通过液态-液态相分离 (LLPS) 形成.
- 维持核细胞完整性的机制,特别是在干细胞中,尚未完全理解.
- N6-甲基氨酸 (m6A) 修饰在各种细胞过程中起作用.
研究的目的:
- 研究METTL3/METTL14复合体在维持人类胚胎干细胞 (hESCs) 中核细胞完整性的作用.
- 阐明METTL3/METTL14调节核细胞结构和功能的分子机制.
主要方法:
- 通过CRISPR-Cas9基因编辑产生METTL3/METTL14缺陷的hESCs.
- 免疫光显微镜用于评估核细胞形态和H3K9me3定位.
- 西方涂抹和免疫沉以分析蛋白质水平和相互作用.
- 蛋白质体活性测定以确认蛋白质降解途径.
主要成果:
- 在hESC中METTL3/METTL14缺乏导致核细胞功能障碍和自我更新的丧失.
- SUV39H1/H2蛋白和H3K9me3标记积聚在METTL3/METTL14缺乏细胞的细胞核中,从而影响LLPS.
- METTL3/METTL14复合物招募CRL4 E3泛酸酶以准SUV39H1/H2进行降解,防止H3K9me3的积累.
结论:
- METTL3/METTL14复合体对于维持hESCs中核细胞完整性至关重要.
- 该复合物通过控制SUV39H1/H2蛋白水平和H3K9me3修饰来调节核细胞完整性.
- 这项研究揭示了一种新的机制,将m6A修饰和表观遗传调节与通过核细胞平衡维持干细胞联系起来.
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