灵活的调解者作为促进者与增强者之间的功能性而不是架构性桥梁
Laila El Khattabi1, Haiyan Zhao2, Jens Kalchschmidt1
1Lymphocyte Nuclear Biology, NIAMS, NIH, Bethesda, MD 20892, USA.
Cell
|August 13, 2019
概括
哺乳动物媒介 (mMED) 对于基因转录至关重要. 这项研究揭示了mMED作为一个功能性桥梁,而不是一个架构性的桥梁,通过其可适应的结构来整合监管信号.
科学领域:
- 分子生物学
- 遗传学
- 结构生物学
背景情况:
- 中介复合体对于真核转录至关重要,但其确切的作用机制仍然不太清楚.
- 了解调解者的作用是解读基因调节过程的关键.
研究的目的:
- 阐明哺乳动物调解器 (mMED) 的功能和结构.
- 研究特定的调解子单元在转录和DNA组织中的作用.
主要方法:
- 基因查CRISPR-Cas9
- 德格朗测试
- 对全基因组相互作用的Hi-C
- 用于结构分析的冷电子显微镜 (cryo-EM)
主要成果:
- 确定了Pol II在整个基因组中的重要调解子单位.
- 证明调解器不需要物理绑定调节DNA.
- 低温电磁检测显示了一个保存的核心和调节尾部模块结构的非必需子单元.
- 尾部模块的结构变化会影响与Pol II和酶模块的相互作用.
结论:
- 哺乳动物中介器作为信号集成器和发射器,作为调节元件和转录机器之间的功能性桥梁.
- 中介的结构可塑性对于其在基因调节中的作用至关重要,而不是DNA组织.
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