(A) Top - LNAR' Enz-sensitive and LREX' Enz-resistant cell lines were derived from in vivo xenograft experiments. Bottom - Flow cytometry on LNAR' and LREX' cell lines for GR expression in the presence and absence of Enz (1 uM). (B) ChIP-seq tracks for H3K27ac (blue), H3K4me1 (green), H3K4me3 (red) at the GR (NR3C1) locus for LNAR', LREX' and LREX'Enz cell lines define the promoter and enhancer regions. Normalized ChIP-seq read counts at GR enhancer/promoter region (LNAR', LREX', LREX'Enz; **=Z score>2): H3K27ac (20.86, 30.57, 72.46**); H3K4me1 (59.62, 36.69, 42.61); H3K4me3 (7.97, 24.54, 94.91**). (C) Top - Experimental design depicting two CRISPR guide pairs (sgGRe_1 and sgGRe_2) flanking the GR (NR3C1) enhancer to excise the entire enhancer region. Bottom - RT-qPCR for GR expression from sorted cells transfected with two different CRISPR guide pairs (sgGRe_1 and sgGRe_2) and a non-targeting (sgNT) control. (D) ChromHMM prediction of promoter and enhancer regulatory elements at the GR (NR3C1) locus using ChIP-seq data for H3K27ac, H3K4me1, H3K4me3 across multiple tissue types (from Roadmap Epigenomics Project), cell lines (from ENCODE database), and prostate cell and organoid lines.