通过RFX5扩展的DNA结合域的核细胞结合和不稳定性的结构基础
Wanqiang Xue1, Yaoyao Han2,3, Ying Tian1
1Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
Nucleic acids research
|July 31, 2025
概括
调节因子X5 (RFX5) 结合核细胞,重塑它们,从而可能增加DNA可访问性和基因转录. 这项研究揭示了RFX5-核酶体结构及其破坏稳定的作用.
科学领域:
- 结构生物学 结构生物学
- 分子生物学分子生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 调节因子X5 (RFX5) 是一种转录因子,与各种疾病有关.
- RFX5的独特之处在于它能够结合核细胞并诱导体内重塑的能力.
研究的目的:
- 使用冷EM确定RFX5-核酶组合物的结构.
- 阐明RFX5与核细胞相互作用并重塑核细胞的机制.
主要方法:
- 低温电子显微镜 (cryo-EM) 用于确定RFX5-核体复合物的结构.
- 结构分析RFX5与核细胞DNA和组织蛋白结合.
主要成果:
- RFX5的扩展DNA结合域 (eDBD) 在超螺旋位置+2.2与核细胞结合.
- RFX5 eDBD与核体DNA和基因组蛋白广泛相互作用.
- 结合RFX5诱导DNA扭曲和隔壁DNA旋转的脱离,破坏核细胞的稳定.
结论:
- 结合RFX5会改变细胞核的结构,从而可能增加DNA的可访问性.
- 这些发现提供了关于RFX5介导的核酶体破坏稳定及其在基因调节中的作用的见解.
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