A dominant-negative SOX18 mutant disrupts multiple regulatory layers essential to transcription factor activity

Jieqiong Lou, Alex McCann, Mehdi Moustaqil, Matthew Graus, Ailisa Blum, Frank Fontaine, Hui Liu, Winnie Luu, Peter Koopman, Emma Sierecki, Yann Gambin, Frédéric Meunier, Zhe Liu, Elizabeth Hinde & Mathias Francois
Few genetically dominant mutations involved in human disease have been fully explained at the molecular level. In cases where the mutant gene encodes a transcription factor, the dominant-negative mode of action of the mutant protein is particularly poorly understood. Here, we studied the genome-wide mechanism underlying a dominant-negative form of the SOX18 transcription factor (SOX18RaOp) responsible for both the classical mouse mutant Ragged Opossum and the human genetic disorder Hypotrichosis-Lymphedema-Telangiectasia-Renal Syndrome. Combining three single-molecule imaging...
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