DUX4 is a transcription factor that contains two tandemly repeated homeodomains (HD1 and HD2) separated by a short linker region. HD1 is responsible for the specific DNA binding activity of DUX4 and binds to the core sequence of 5’ TAAT 3’. Glu 70 (-ve) from HD1 also forms a salt bridge with Arg73 (+ve), which confers the unique DNA sequence specificity to DUX4. HD2 recognizes a different core sequence of 5’ TGAT 3’, despite being a tandem repeat with HD1. The linker region between the two homeodomains is flexible, allowing the two domains to move independently and adopt different orientations. Overall, understanding the structure of DUX4, particularly HD1 and the Glu70-Arg73 salt bridge, provides important insights into the specific DNA recognition and transcriptional regulation by this transcription factor, which is crucial for developing potential therapeutic strategies for DUX4-associated diseases.
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