Epigenetic remodelling during early embryogenesis and gametogenesis involves changes in DNA methylation (5mC), critical for maintaining and driving cell identity in the developing embryo. Surprisingly however, 5mC is targeted to a very small group of gene promoters during embryogenesis and these targets, many of which are implicated in germline formation, are frequently reactivated in human cancers including melanoma and hepatic cancer. These genes mainly correspond to the family of cancer-testis antigens (CTAs). Normally, CTAs are expressed in the germline and have highly restricted expression patterns in somatic tissues. Thus, CTAs harbour excellent potential to be used as tumour vaccines. During oncogenesis, CTA promoters are aberrantly hypomethylated, however the exact contribution of CTA overexpression to oncogenesis remains unclear. Using whole genome bisulfite sequencing of early zebrafish embryos, we have identified 50 gene promoters that are progressively silenced during early embryogenesis via 5mC deposition and exhibit a pattern of expression restricted to the germline in adult tissues. While a number of these genes have been previously identified as CTAs, others can be considered as novel putative CTAs. Comparisons with mammalian 5mC data suggest that this targeted silencing of CTA promoters is one of the most highly conserved epigenome remodelling events observed in vertebrates. Using TCGA database DNA methylation and gene expression data we confirm the aberrant promoter DNA demethylation dynamics as well as aberrant reactivation of a subset of the identified putative CTAs in cancers. We hypothesize that reactivation of these conserved CTAs will contribute to or perhaps even drive a malignant phenotype. We are currently developing zebrafish transgenic tools to be able to test this hypothesis in vivo.