核素-Chd1结构和对染色体重塑的影响
Lucas Farnung1, Seychelle M Vos1, Christoph Wigge1
1Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Am Fassberg 11, 37077 Göttingen, Germany.
Nature
|October 12, 2017
概括
染色体-酶-DNA结合蛋白1 (Chd1) 通过分离DNA并定位其ATPase电机进行转位来重塑核体. 这种结构洞察力揭示了Chd1如何促进DNA转录并维持细胞多能性.
科学领域:
- 分子生物学
- 结构生物学
- 表观遗传学
背景情况:
- 染色体重塑因子对于DNA转录,复制和修复等过程至关重要.
- 保存的染色体-酶-DNA结合蛋白1 (Chd1) 在核体间距,RNA聚合酶II通路和细胞多能性中起作用.
研究的目的:
- 确定酵母Saccharomyces cerevisiae Chd1与核体结合的冷电子显微镜结构.
- 阐明Chd1重塑核体并影响DNA可访问性的机制.
主要方法:
- 在4.8 Å分辨率的冷电子显微镜.
- 对Chd1核酶组的结构分析.
主要成果:
- Chd1将两个DNA旋转从基因组八合体中分离出来,在催化平衡状态下在DNA旋转之间结合.
- 特定的域 (SANT,SLIDE,ATPase电机) 与DNA在定义的超螺旋位置 (SHL) 和基因组H4相互作用.
- 双染色体促进ATPase关闭,使DNA转位和核细胞重塑成为可能.
结论:
- 该结构揭示了Chd1释放DNA旋转和重塑核细胞的机制.
- Chd1的ATPase活性,可能涉及拉切特机制,是其在染色质调节中的关键功能.
- 这为Chd1在转录和多能性中的作用提供了结构基础.
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