Salt Dependence of DNA Binding Activity of Human Transcription Factor Dlx3

• Published in: International journal of molecular sciences 2022-08, Vol.23 (16), p.9497
• Main Authors: Jin, Ho-Seong, Son, Juyeon, Seo, Yeo-Jin, Choi, Seo-Ree, Ahn, Hye-Bin, Go, Youyeon, Lim, Juhee, Oh, Kwang-Im, Ryu, Kyoung-Seok, Lee, Joon-Hwa
• Format: Article
• Language: English
• Subjects: base-pair stability; Binding; Binding sites; Chemical equilibrium; chemical shift perturbation; Conserved sequence; Crystal structure; DNA–protein interaction; Domains; Homeobox; Mutation; NMR; Nucleotide sequence; salt dependence; Titration; transcription factor; Transcription factors
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23169497

Distal-less 3 (Dlx3) is a homeobox-containing transcription factor and plays a crucial role in the development and differentiation process. Human Dlx3 consists of two transactivation domains and a homeobox domain (HD) that selectively binds to the consensus site (5′-TAATT-3′) of the DNA duplex. Here, we performed chemical shift perturbation experiments on Dlx3-HD in a complex with a 10-base-paired (10-bp) DNA duplex under various salt conditions. We also acquired the imino proton spectra of the 10-bp DNA to monitor the changes in base-pair stabilities during titration with Dlx3-HD. Our study demonstrates that Dlx3-HD selectively recognizes its consensus DNA sequences through the α3 helix and L1 loop regions with a unique dynamic feature. The dynamic properties of the binding of Dlx3-HD to its consensus DNA sequence can be modulated by varying the salt concentrations. Our study suggested that this unique structural and dynamic feature of Dlx3-HD plays an important role in target DNA recognition, which might be associated with tricho-dento-osseous syndrome.