Mechanism of forkhead transcription factors binding to a novel palindromic DNA site.

Jun Li, Shuyan Dai, Xiaojuan Chen, Xujun Liang, Lingzhi Qu, Longying Jiang, Ming Guo, Zhan Zhou, Hudie Wei, Huajun Zhang, Zhuchu Chen, Lin Chen, Yongheng Chen

Nucleic acids research 2021 Apr 06

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Forkhead transcription factors bind a canonical consensus DNA motif, RYAAAYA (R = A/G, Y = C/T), as a monomer. However, the molecular mechanisms by which forkhead transcription factors bind DNA as a dimer are not well understood. In this study, we show that FOXO1 recognizes a palindromic DNA element DIV2, and mediates transcriptional regulation. The crystal structure of FOXO1/DIV2 reveals that the FOXO1 DNA binding domain (DBD) binds the DIV2 site as a homodimer. The wing1 region of FOXO1 mediates the dimerization, which enhances FOXO1 DNA binding affinity and complex stability. Further biochemical assays show that FOXO3, FOXM1 and FOXI1 also bind the DIV2 site as homodimer, while FOXC2 can only bind this site as a monomer. Our structural, biochemical and bioinformatics analyses not only provide a novel mechanism by which FOXO1 binds DNA as a homodimer, but also shed light on the target selection of forkhead transcription factors. © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

Citation

Jun Li, Shuyan Dai, Xiaojuan Chen, Xujun Liang, Lingzhi Qu, Longying Jiang, Ming Guo, Zhan Zhou, Hudie Wei, Huajun Zhang, Zhuchu Chen, Lin Chen, Yongheng Chen. Mechanism of forkhead transcription factors binding to a novel palindromic DNA site. Nucleic acids research. 2021 Apr 06;49(6):3573-3583