Epigenetic marks remain dynamic in most somatic cells to enable flexible gene activity. Simultaneously, this creates a cellular environment prone to “epigenetic mistakes” and this is most evident in diseases such as cancer. It is well established that cancer initiation and progression is caused by a complex series of genetic and epigenetic changes encompassing altered patterns of DNA methylation, histone modifications and the physical chromatin structure (e.g. nucleosome positions and higher-order chromatin). The ultimate consequence of these collective changes is an abnormal gene expression signature that acts as a catalyst for disease. We have utilized a model of normal prostate epithelial cells (PrEC) and two metastatic prostate cancer cell lines (LNCaP and PC3), and have examined common and rare transcriptomic changes including alternative splicing, exon skipping, differential gene expression and enhancer transcripts. Integration of these data with nucleosome occupancy and methylation sequences will enable us to determine whether nucleosome positioning is likely to play a role in all or some of these transcriptomic changes.