Histone demethylase UTY (UTY)

Histone demethylase UTY is a Y-chromosome-encoded enzyme in humans responsible for catalyzing the demethylation of trimethylated lysine 27 on histone H3 (H3K27me3), although it has significantly lower catalytic activity compared to its X chromosome homolog KDM6A (UTX)[4][5]. UTY contains tetratricopeptide repeat domains implicated in protein–protein interactions and plays a role in chromatin organization and epigenetic gene regulation. It is male-specific and also functions as a minor histocompatibility antigen, which can trigger immune responses leading to graft rejection in male-to-female stem cell transplantation[3]. While it is enzymatically active in vitro, its activity is lower and possibly more target-selective in cells compared to KDM6A[4][5]. Emerging studies indicate UTY may also contribute to gene regulation via demethylase-independent mechanisms[1]. Its dysfunction or misregulation has been implicated in developmental anomalies and cancer, and its antigenicity is clinically notable in transplantation settings[1][3][4].

Other names

KDM6CKDM6ALUbiquitously transcribed tetratricopeptide repeat protein on the Y chromosomeUbiquitously transcribed TPR gene on Y chromosomeUbiquitously transcribed tetratricopeptide repeat gene, Y-linkedUbiquitous TPR motif protein UTYMinor histocompatibility antigen UTY[Histone H3]-trimethyl-L-lysine(27) demethylase UTY

Inhibition of UTY would be expected to increase histone H3K27 methylation, promoting transcriptional repression at specific loci[4][5].