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

The study investigated the molecular basis of the nude phenotype, characterized by alopecia and thymic aplasia, in humans and rodents. It identified Whn, a forkhead/winged-helix transcription factor, as crucial for regulating hair keratin gene expression. In HeLa cells, Whn induced expression of human hair keratin genes Ha3-II and Hb5, while nude mice with a Whn loss-of-function mutation showed reduced expression of corresponding mouse genes. A specific nude allele, nu(Y), had a mutation in Whn's DNA binding domain, impairing its function. Experiments demonstrated that Whn's ability to activate hair keratin genes depended on the structural integrity and proximity of its DNA binding and activation domains. This research highlighted Whn's role as a transcriptional regulator of hair keratin genes and identified the nude phenotype as an inherited skin disorder caused by loss of gene expression rather than keratin gene mutation.