Xue Wanqiang, Han Yaoyao, Tian Ying, Wang Junzheng, Xie Zhiyuan, Zheng Xin, Yue Xue, Dong Siqi, Li Huimin, Luo Zhen, Zhang Siqiu, Yang Ying, Zou Zhe, Li Wei, Ma Nana, Zhu Fangjie, Chen Chunlai, Yin Yimeng, Zhang Yixiao, Xu Ke
Shanghai 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.
Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China.
Nucleic Acids Res. 2025 Jul 19;53(14). doi: 10.1093/nar/gkaf734.
Among the regulatory factor X (RFX) transcription factor family, RFX5 is uniquely reported to bind nucleosomes and induce nucleosome remodeling in vivo. Dysfunctions in RFX5 have been implicated in various diseases. Here, we present the cryogenic electron microscopy (cryo-EM) structure of the RFX5-nucleosome complex, revealing that the extended DNA binding domain (eDBD) of RFX5 binds to the nucleosome at superhelical location +2. RFX5 eDBD engages not only with nucleosomal DNA but also with histones through extensive interactions. Compared to the structure of a free nucleosome, RFX5 eDBD induces localized distortion of the bound DNA gyre and detachment of the adjacent DNA gyre in the RFX5-nucleosome complex. This structural alteration could potentially increase DNA accessibility and enhance transcriptional activity in vivo. Overall, our study provides novel insights into the mechanisms by which RFX5 eDBD interacts with and destabilizes nucleosomes.
在调节因子X（RFX）转录因子家族中，有独特报道称RFX5可在体内结合核小体并诱导核小体重塑。RFX5功能障碍与多种疾病有关。在此，我们展示了RFX5-核小体复合物的低温电子显微镜（cryo-EM）结构，揭示RFX5的延伸DNA结合结构域（eDBD）在超螺旋位置+2处与核小体结合。RFX5 eDBD不仅通过广泛相互作用与核小体DNA结合，还与组蛋白结合。与游离核小体的结构相比，RFX5 eDBD在RFX5-核小体复合物中诱导结合的DNA螺旋局部扭曲以及相邻DNA螺旋分离。这种结构改变可能会增加体内DNA的可及性并增强转录活性。总体而言，我们的研究为RFX5 eDBD与核小体相互作用并使其不稳定的机制提供了新见解。
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