Cancer is characterised by changes in gene expression commonly mediated by epigenetic and genetic lesions. We previously discovered that epigenetic deregulation occurs not only at single genes but can also encompass large chromosomal domains in cancer 1. We also found that nuclear architecture is disrupted to form both repressive and active cancer domains, by processes we termed Long Range Epigenetic Silencing (LRES) 2 and Long Range Epigenetic Activation (LREA) 3. However the underlying mechanisms involved in regional remodelling are still poorly understood. Our preliminary data suggests that the spatial arrangement of chromatin could play a role in this deregulation as we show that some LRES and LREA domains are demarked by the boundary element CTCF. We propose that CTCF acts as an insulator that prevents the inappropriate spread of heterochromatin structures and also facilitates chromatin looping which can determine regulatory factors such as promoter accessibility and enhancer/promoter interactions. Therefore CTCF potentially influences gene expression through modulation of chromatin conformation. To address if deregulation of nuclear architecture and loss of boundary elements contribute to long range epigenetic alterations in prostate cancer we are performing both transient and stable knockdowns of CTCF in LNCaP prostate cancer cells using either siRNA pools or a vector containing shRNA against CTCF and an antibiotic selection marker. To then determine if there are regional changes in gene expression across LREA and LRES domains, associated with disrupted CTCF expression, we are performing Affymetrix Gene Arrays 2.0ST on knockdown and control cells. Here, we will present our results that suggest that CTCF is a critical component in regulation or demarcation of regional compartments of the cancer epigenome.