福克萨2和H2A.Z在胚胎干细胞分化过程中调解核素体枯竭
Zhaoyu Li1, Paul Gadue, Kaifu Chen
1Department of Genetics and Institute of Diabetes, Obesity and Metabolism, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Cell
|December 25, 2012
概括
这项研究揭示了胚胎干细胞 (ES) 在内皮分化过程中核细胞动力学是如何控制的. 表观遗传和遗传因素,如DNA甲基化和基因组变异H2A.Z调节染色质重塑细胞命运决定.
科学领域:
- 表观遗传学和发育生物学
- 染色体生物学 染色体生物学
- 干细胞分化的过程
背景情况:
- 核细胞占用对于染色体结构至关重要.
- 与早期细胞谱系规范联系核细胞组动态的机制尚不清楚.
研究的目的:
- 研究胚胎干细胞 (ES) 在内皮分化过程中控制全球核酶体动态的机制.
- 阐明表观遗传和遗传因素在这个过程中的作用.
主要方法:
- 在ES细胞分化过程中核细胞占用率变化的分析.
- 调查基因组变异H2A.Z,转录因子Foxa2和DNA甲基化的作用.
- 评估SWI/SNF和INO80染色体重塑复合物的参与.
主要成果:
- 在分化过程中发生核缩和de novo占用,在分化后密度增加.
- 基因组H2A.Z和Foxa2促进核细胞体枯竭和基因激活.
- 基因甲基化驱动核酶体的占用和基因抑制.
- 核细胞体枯竭取决于Nap1l1合的SWI/SNF和INO80复合体.
结论:
- 两种表观遗传 (DNA甲基化) 和遗传 (H2A.Z,Foxa2) 调节者都合作控制核细胞的动态.
- 这些动态对于在ES细胞命运决定和内皮分化过程中调节基因表达至关重要.
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