Sox2与DNA的长期结合预测了四细胞小鼠胚胎中的细胞命运
Melanie D White1, Juan F Angiolini2, Yanina D Alvarez2
1Institute of Molecular and Cell Biology, A(∗)STAR, 61 Biopolis Drive, Singapore 138673, Singapore.
Cell
|March 26, 2016
概括
转录因子 (TF) 的DNA结合动态预测细胞命运. 在小鼠胚胎中,由H3R26甲基化调节的Sox2结合稳定性预测了从四细胞阶段开始的多能细胞发展.
科学领域:
- 发育生物学
- 表观遗传学
- 分子生物学
背景情况:
- 转录因子 (TF) 的DNA结合对基因调节至关重要.
- 在体内细胞命运测定过程中对TF-DNA相互作用的理解是有限的.
研究的目的:
- 在小鼠胚胎发育过程中量化单细胞的TF-DNA结合动力学.
- 研究TF-DNA结合,表观遗传修饰和细胞命运决定之间的关系.
主要方法:
- 使用可光激活光相关谱 (FCS) 来测量单细胞中的TF-DNA结合.
- 使用活细胞追踪来将结合动态与细胞系和后代相关联.
- 研究了H3R26甲基化在调节TF-DNA相互作用中的作用.
主要成果:
- 在胚胎细胞中,多能细胞和胚胎外细胞之间的Oct4和Sox2结合稳定性不同.
- 在早期胚胎中,Sox2表现出比Oct4更长寿命的DNA相互作用.
- Sox2的长寿命结合在胚芽细胞之间有所不同,并通过H3R26甲基化进行调节.
- 具有更稳定的Sox2结合的芽细胞产生更多的多能后代.
- 减少H3R26甲基化会减少Sox2结合,目标基因表达和多能细胞数量.
结论:
- 在Sox2-DNA结合的动态预测哺乳动物细胞的命运早在四细胞阶段.
- 生理表观遗传变化在DNA位点之间动态分配TF.
- H3R26甲基化是Sox2结合和多能性维持的关键调节剂.
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