Ligand-Independent Regulation of the Hairless Promoter by Vitamin D Receptor

The study investigated the relationship between the vitamin D receptor (VDR) and the hairless (hr) gene, both of which are implicated in hair loss disorders such as atrichia and VDRRIIa rickets. The researchers found that VDR can repress the activity of the hr promoter in both HaCaT cells and primary human keratinocytes (PHKs), even in the absence of its ligand, 1,25 dihydroxyvitamin D3 (D3). The repression is enhanced with the addition of D3. Interestingly, they also discovered that VDR can activate the hr promoter without the ligand, but this effect is cell type-specific. These findings suggest that VDR's direct transcriptional regulation of the hr gene may contribute to the similar hair loss phenotypes observed in atrichia and VDRRIIa rickets.