Investigations Into The Role Of The X-Linked Epigenetic Regulator UTX (KDM6A) In Self-Renewing Stratifying Epithelia
January 2025
in “
Scholarly Commons (University of Pennsylvania)
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TLDR UTX is important for skin health and its loss can lead to skin issues, especially in females.
The study investigates the role of the X-linked histone demethylase UTX (KDM6A) in skin differentiation and its regulation of retinoic acid (RA) signaling, crucial for skin homeostasis and treatment of various skin conditions. UTX deletion in the skin affects genes involved in epidermal stem cell fate and differentiation, leading to dysregulation in epidermal, sebaceous, and hair follicle differentiation, particularly in homozygous females. This suggests that UTX's function is primarily non-catalytic, as its Y-linked paralog UTY compensates in males. The loss of UTX results in persistent inflammation similar to RA signaling loss, with potential immune activation due to apoptotic debris in hair follicles. Utx-cKO female mice show increased susceptibility to psoriasis, highlighting the relevance of UTX in sex-biased skin diseases. The findings suggest that epigenetic modulation of signaling pathways could be a strategy for treating skin diseases, considering sex disparities.