Interactions of the Vitamin D Receptor with the Corepressor Hairless

The document from August 1, 2007, investigated the interaction between the Vitamin D Receptor (VDR) and mutants of the Hairless (HR) gene, which is associated with atrichia with papular lesions (APL), a form of hair loss. The study found that most pathogenic HR mutants lost their corepressor activity on VDR, which could be due to impaired interactions with histone deacetylase 1 (HDAC1). However, one mutant, E583V, retained normal activity, suggesting it may not be pathogenic. HR variants from non-synonymous polymorphisms showed normal or partially reduced corepressor activity. All pathogenic mutants and variants increased the level of VDR protein when coexpressed, indicating that this HR function was not affected by the mutations. The study provided insight into the molecular basis of APL by showing how HR mutations impact VDR corepressor activity.