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

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 0, 1, 24 and 96 hours were analyzed by TruSeq Methyl Capture sequencing. Raw sequencing reads were aligned to the human genome (hg19) and methylation levels called using bismark.