Forkhead/Winged-Helix Transcription Factor Whn Regulates Hair Keratin Gene Expression: Molecular Analysis of the Nude Skin Phenotype

The study explored the role of the Whn transcription factor in hair keratin gene expression, using HeLa cells and nude mice models. Whn was essential for the expression of hair keratin genes, as its absence in nude mice led to reduced keratin gene expression and hair shaft defects. In HeLa cells, Whn upregulated basic hair keratin genes, indicating its role as a general regulator. The study identified a critical DNA-binding domain necessary for Whn function, with mutations in this domain preventing gene activation. The research provided a molecular explanation for the nude phenotype in mice, linking it to Whn dysfunction rather than keratin gene mutations, and highlighted a complex regulatory network involving cofactors like LEF-1 and Hoxc13.