Epigenetic deregulation is involved in cancer initiation and progression, but most studies have concentrated on gene repression and hypermethylation of tumour suppressor genes. Therefore the mechanism underpinning epigenetic-based gene activation in carcinogenesis is still poorly understood.  We reported that epigenetic changes could occur over large domains, resulting in concordant gene repression by Long Range Epigenetic Silencing (LRES) and more recently we reported that concordant gene activation by Long Range Epigenetic Activation (LREA)¹ of multiple adjacent genes also is common in cancer.  By an integrative epigenome-wide sequencing analysis of prostate cancer and normal cells, we found the epigenetic deregulated domains are characterised by an exchange of active (H3K9ac and H3K4me3) chromatin marks, and repressive (H3K9me2 and H3K27me3) marks.  Notably, whilst promoter hypomethylation did not often contribute to gene activation, extensive DNA hypermethylation of CpG islands or “CpG island borders” was strongly related to both gene repression and cancer-specific gene activation or a change in promoter usage.  We also found that the epigenetic deregulated domains change in the replication timing in cancer, with a clear shift to late replication in LRES regions and conversely early replication in LREA regions. These findings have wide ramifications for cancer diagnosis, progression and epigenetic-based gene therapies.