Dynamic patterns of DNA methylation in the normal prostate epithelial differentiation program are targets of aberrant methylation in prostate cancer

Understanding the epigenetic control of normal differentiation programs might yield principal information about critical regulatory states that are disturbed in cancer. We utilized the established non-malignant HPr1-AR prostate epithelial cell model that upon androgen exposure commits to a luminal cell differentiation trajectory from that of a basal-like state. We profile the dynamic transcriptome associated with this transition at multiple time points (0hr, 1hr, 24hr, 96hr), and confirm that expression patterns are strongly indicative of a progressive basal to luminal cell differentiation program based on human expression signatures. Furthermore, we establish dynamic patterns of DNA methylation associated with this program by use of whole genome bisulfite sequencing (WGBS). Overall design: HPr1-AR cells exposed to DHT (10nM) for 1, 24 and 96 hours were analyzed by RNA-seq. Sequenced samples were aligned to the human genome (hg19) using tophat2, and aligned reads translated to expression counts via featurecounts, followed by a standard DESeq2 pipeline for data normalization and differential expression analysis.