ChIP-seq analysis of H3K4me3 and H3K27me3 histone modification in MBT2 cell lines transfected pX330 vector with Utx-targeted sgRNA ( KO) or without Utx-targeted sgRNA ( EV). Mus musculus

UTX (Ubiquitously transcribed tetratricopeptide repeat, X chromosome, also known as KDM6A) mutations are frequently found in urologic tumors including BC, strongly suggesting that UTX plays fundamental roles in the homeostasis of the urinary system. However, the molecular mechanisms through which functional loss of UTX contributes to BC pathogenesis remain to be fully clarified. To address this issue, we generated mice with bladder urothelium-specific deletion of UTX. In addition, to analyze the multistep process of BC carcinogenesis, the Utx-deficient mice were crossed with heterozygous mice for p53, whose mutation/deletion is frequently overlapped with Utx mutation, and were exposed to BBN. Gene set enrichment analysis using urothelium from those mice revealed that Utx deficiency activates cytokine/chemokine signaling. UTX catalyzes H3K27 demethylation per se and also functions as a component of COMPASS-like complex that promotes H3K4 methylation. Therefore we conducted ChIP-seq analysis to clarify the relationship between H3K4me3/H3K27me3 histone modification and the activation of cytokine/chemokine signaling.