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TitleStructural basis of nucleosome binding and destabilization by the extended DNA binding domain of RFX5.
Journal, issue, pagesNucleic Acids Res, Vol. 53, Issue 14, Year 2025
Publish dateJul 19, 2025
AuthorsWanqiang Xue / Yaoyao Han / Ying Tian / Junzheng Wang / Zhiyuan Xie / Xin Zheng / Xue Yue / Siqi Dong / Huimin Li / Zhen Luo / Siqiu Zhang / Ying Yang / Zhe Zou / Wei Li / Nana Ma / Fangjie Zhu / Chunlai Chen / Yimeng Yin / Yixiao Zhang / Ke Xu /
PubMed AbstractAmong 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 ...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.
External linksNucleic Acids Res / PubMed:40744500 / PubMed Central
MethodsEM (single particle)
Resolution3.2 - 3.3 Å
Structure data

60154

8zjr

EMDB-60154, PDB-8zjr:
Structure of nucleosome-bound RFX5 complex
Method: EM (single particle) / Resolution: 3.3 Å

60156

8zjt

EMDB-60156, PDB-8zjt:
Structure of free nucleosome
Method: EM (single particle) / Resolution: 3.2 Å

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsSTRUCTURAL PROTEIN/DNA / Nucleosome / histone / DNA / STRUCTURAL PROTEIN-DNA complex

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