Fig. 2: PRC2 targets are distinct in PRAD and NEPC.
From: Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes
A Schematic of rapid autopsy sites of NEPC and castrationresistant PRAD and workflow of H3K27me3 CUT&Tag and downstream differential analysis. Figure 2/panel A Created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license. B H3K27me3 fragment per million (FPM) reads were calculated genome-wide for 10 kb bins for each sample. Principal component analysis of the FPM values from PRAD and NEPC samples across two dimensions; pale pink, castration resistant PRAD; burgundy, NEPC. C Volcano plot with differentially enriched 10 kb bins of H3K27me3 FPM values in NEPC or castration resistant PRAD samples; blue, H3K27me3 regions enriched in NEPC samples; red, H3K27me3 regions enriched in castration resistant PRAD samples; burgundy, NE-lineage transcription factors with enrichment of H3K27me3 at either promoter or gene body. D Bar plot showing distribution of subtype specific H3K27me3 enriched in castration resistant PRAD or NEPC; light blue, promoter; blue, 5’ untranslated regions (UTR); green, 3’ UTR; pale pink, 1st exon; coral, other exon; orange, 1st exon; violet, other intron; gray, downstream ( < 3 kb); brown, distal intergenic. E Gene ontology analysis of transcription factors with enrichment of H3K27me3 in the promoter of gene body from in castration resistant PRAD (C) with p-value < 0.05 and Log2FoldChange > 0; size, -log10FDR; orange-black gradient, gene ratio. F Screenshots from Integrative Genomics Viewer (IGV) of CUT&Tag H3K27me3 levels in castration resistant PRAD and NEPC and the genomic loci of indicated NE-lineage genes (ASCL1, PROX1, NEUROD1, LHX2, FOXA2, POU3F2, INSM1); pale pink, castration resistant PRAD samples; burgundy, NEPC samples. G Screenshots from Integrative Genomics Viewer (IGV) of CUT&RUN H3K27me3 levels in LNCaP-abl and WCM154 and the genomic loci of indicated NE-lineage genes; gray, IgG; red, H3K27me3. H Pearson’s product-moment correlation of Log2FoldChange of H3K27me3 FPM values in PRAD (n = 9) compared to NEPC (n = 9) in Clinical CUT&Tag in this study vs LuCaP ChIP-Seq (PRAD; n = 5, NEPC; n = 5) from Baca et al.31 (publicly available in Gene Expression Omnibus under accession code: GSE161948); teal, genome-wide 10 kb regions; brown, all significantly altered regions (PRAD vs NEPC) common in both datasets.
