UTX (KDM6A) Promotes Differentiation Noncatalytically in Somatic Self-Renewing Epithelia

This study examines the role of UTX (KDM6A) in skin differentiation, emphasizing its noncatalytic functions in regulating retinoic acid (RA) signaling, which is crucial for skin homeostasis. The research shows that UTX is essential for activating skin differentiation gene expression, with its absence leading to disrupted epidermal, sebaceous, and hair follicle differentiation, particularly in females due to compensation by the Y-linked paralog UTY in males. UTX deficiency results in a sex-biased cutaneous phenotype, including skin reddening, hair thinning, and epidermal hyperplasia in females. The study highlights the loss of H3K27 acetylation and impaired RA signaling, suggesting UTX's role as a key epigenetic regulator. These findings provide insights into potential therapeutic pathways for skin diseases and underscore the importance of UTX in maintaining skin health.