Kang et al. discovered that the de novo methylation of CpG islands in the promoter regions is an epigenetic mark of gene silencing in cancer; DNA methylation disrupts the proper chromatin loops of the PTGS2 locus by limiting the binding of CTCF/cohesin to the PTGS2 locus, which subsequently reduces the PTGS2 expression [30]. Here, CTCF is linked to cancer.