The <i>hairless</i> gene mutated in congenital hair loss disorders encodes a novel nuclear receptor corepressor

The study revealed that the mammalian hairless (hr) gene, crucial for hair growth maintenance, encoded a protein (Hr) functioning as a transcriptional corepressor for thyroid hormone receptors (TRs). Hr interacted with TRs through two independent regions, utilizing hydrophobic residues similar to those in known nuclear receptor corepressors. It also associated with histone deacetylases (HDACs) and localized to matrix-associated deacetylase bodies, suggesting repression through HDAC activity. Despite lacking sequence identity with other corepressors, Hr's action was conserved, indicating it as a new class of nuclear receptor corepressors with specialized roles. This discovery provided a molecular basis for specific hair loss syndromes in humans and mice.