Structural basis of nucleosome binding and destabilization by the extended DNA binding domain of RFX5
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.
Authors
- Nana Ma
- Yimeng Yin (ORCID: https://orcid.org/0000-0002-5454-608X)
- Ying Yang (ORCID: https://orcid.org/0000-0002-6049-401X)
- Huimin Li (ORCID: https://orcid.org/0000-0001-6660-7620)
- Yingjie Tian (ORCID: https://orcid.org/0000-0002-4675-0398)
- Fangjie Zhu (ORCID: https://orcid.org/0000-0002-0143-5765)
- Yue Xue (ORCID: https://orcid.org/0000-0003-2104-120X)
- Zhen‐Ge Luo (ORCID: https://orcid.org/0000-0001-5037-0542)
- Zhiyuan Xie (ORCID: https://orcid.org/0000-0001-6081-2033)
- Chunlai Chen (ORCID: https://orcid.org/0000-0002-0128-7766)
- Shuai Zhang (ORCID: https://orcid.org/0000-0001-5435-2640)
- Weichen Xue (ORCID: https://orcid.org/0000-0002-9779-5676)
- Junzheng Wang
- Yixiao Zhang (ORCID: https://orcid.org/0000-0003-1540-4334)
- Wei Li (ORCID: https://orcid.org/0000-0001-6728-1300)
- Siqi Dong (ORCID: https://orcid.org/0000-0001-6928-2761)
- Ke Xu (ORCID: https://orcid.org/0000-0001-7552-5002)
- Yaoyao Han (ORCID: https://orcid.org/0009-0007-6725-6894)
- Xin Zheng (ORCID: https://orcid.org/0000-0003-1384-6999)
- Zhe Zou
Institutions
- Shanghai Institute of Organic Chemistry (CN)
- Shanghai East Hospital (CN)
- Center for Life Sciences (CN)
- Shanghai Center for Brain Science and Brain-Inspired Technology (CN)
- Fujian Agriculture and Forestry University (CN)
Publication Details
- Journal
- Nucleic Acids Research
- Published
- 2025-07-19
- DOI
- https://doi.org/10.1093/nar/gkaf734
- Citations
- 2
- Primary Topic
- Genomics and Chromatin Dynamics
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities