Fig. 5: ZMYND11 induces AR signaling pathway and represses ERG activity.

a, b Immunoblot of indicated proteins (n = 2) (a) and corresponding 2D proliferation assay (b) of VCaP cancer cells overexpressing HA-ZMNYD11-WT and derived degron-deficient mutants (DMT1/2) (n = 3). Correlation between cell viability and ZMYND11 protein expression changes (Prot. Exp. Changes), as quantified by immunoblot in the same cell lines. P-values were calculated using the Pearson rank correlation. c Fold-change cell viability of VCaP cancer cells overexpressing the indicated SPOP species with and without ZMYND11 knockdown using two different short-hairpin RNAs, at day 16 (n = 3) one-way ANOVA with multiple comparisons and adjusted using Benjamini–Hochberg post-test. The protein expression of the indicated proteins was analyzed by immunoblotting. d Chord-diagram of transcriptionally regulated genes by either SPOP-MTs or HA-ZMYND11-DMT2 in VCaP cells (FDR < 0.05). Strings, whose thickness is proportional to the number of shared elements, represent common genes between sets. e Gene-set enrichment analysis of VCaP cell overexpressing HA-ZMYND11-DMT2 compared to Control, based on RNA-seq data. Enrichments are performed on custom gene-sets of direct androgen receptor (AR) and ERG target genes. FDR-adjusted P-values are computed with Camera (pre-ranked). f Heatmap of ChIP-seq signals around TSS regions (+/−4 kb) at which ZMYND11 bindings were identified by peak calling procedure (Macs2) in VCaP cells overexpressing the indication constructs. g IGV-derived screenshots representing loglikelihood ratio of ZMYND11 bindings in mutant SPOP (SPOP-Y87C) vs. wild-type SPOP over-expressing VCaP cells. Reported are MYC (up) and CDKN1A (bottom). All error bars, mean ± s.e.m. P-values were determined by two-way ANOVA (b Molecular weights are indicated in kilodaltons (kDa). Source data are provided as a Source Data File.