Extended Data Fig. 4: Motif characterization of the NSD2-enabled AR neo-cistrome in prostate cancer cells.
From: NSD2 is a requisite subunit of the AR/FOXA1 neo-enhanceosome in promoting prostate tumorigenesis
a) Left: Schematic representation of the half-motif enrichment analysis. Right: Motif enrichment plot of AR half-motifs with neighboring motifs of other transcription factors at NSD2-dependent and independent AR sites in LNCaP cells. b) Venn diagram showing overlaps between AR ChIP-seq sites in LHSAR cells with LacZ (control), FOXA1, HOXB13, FOXA1 + HOXB13 overexpression. c) Venn diagram showing overlap of AR cistromes (ChIP-seq) in normal prostate, primary prostate cancer, and castration-resistant prostate cancer specimens. (Pomerantz et. al.5,6). d) Motif fold-change heatmap in normal, primary cancer, and castration-resistant prostate cancer specimens. e) Fold-change and significance of HOMER motifs enriched within mCRPC cancer-specific AR sites over normal tissue-specific AR elements (data from Pomerantz5,6). f) Barplot showing percentage of shared sites between the NSD2-dependent AR sites and AR cistromes from the normal prostate, primary PCa (T-ARBS), or metastatic CRPC (met-ARBS) patient tumors. g) Box plot showing H3K27ac ChIP-seq read density at sites containing the ARE or the FOXA1:AR motif in normal and tumor patient samples (normal prostate, n = 7; primary prostate cancer, n = 13; castration-resistant prostate cancer - CRPC, n = 15; one-way ANOVA and Tukey’s test). Box plot center, median; box, quartiles 1-3; whiskers, quartiles 1-3 ± 1.5 × interquartile range; dot, outliers. h) ChIP-seq read-density tracks of AR and H3K27ac within the SLC45A3 and TMPRSS2 loci in NSD2 WT and NSD2-KO LNCaP cells. Super-enhancer clusters are highlighted in a gray box.
