Epigenetics integrates genomic and environmental information to produce a given phenotype. Here, the model of Conserved Epigenetic Regulation of Sex (CERS) is discussed. This model is based on our knowledge on genes involved in sexual development and on epigenetic regulation of gene expression activation and silencing. This model was recently postulated to be applied to the sexual development of fish, and it states that epigenetic and gene expression patterns are more associated with the development of a particular gonadal phenotype, e.g., testis differentiation, rather than with the intrinsic or extrinsic causes that lead to the development of this phenotype. This requires the existence of genes with different epigenetic modifications, for example, changes in DNA methylation levels associated with the development of a particular sex. Focusing on DNA methylation, the identification of CpGs, the methylation of which is linked to sex, constitutes the basis for the identification of Essential Epigenetic Marks (EEM). EEMs are defined as the number and identity of informative epigenetic marks that are strictly necessary, albeit perhaps not sufficient, to bring about a specific, measurable, phenotype of interest. Here, we provide a summary of the genes where DNA methylation has been investigated so far, focusing on fish. We found that cyp19a1a and dmrt1, two key genes for ovary and testis development, respectively, consistently show an inverse relationship between their DNA methylation and expression levels, thus following CERS predictions. However, in foxl2a, a pro-female gene, and amh, a pro-male gene, such relationship is not clear. The available data of other genes related to sexual development such as sox9, gsdf, and amhr2 are also discussed. Next, we discuss the use of CERS to make testable predictions of how sex is epigenetically regulated and to better understand sexual development, as well as the use of EEMs as tools for the diagnosis and prognosis of sex. We argue that CERS can aid in focusing research on the epigenetic regulation of sexual development not only in fish but also in vertebrates in general, particularly in reptiles with temperature sex-determination, and can be the basis for possible practical applications including sex control in aquaculture and also in conservation biology.

The marine environment is predicted to become warmer and more hypoxic, and these conditions may become a challenge for marine fish species. Phenotypically plastic responses facilitating acclimatization to changing environments can be mediated by DNA methylation through the modulation of gene expression. To investigate whether temperature and hypoxia exposure induce DNA methylation changes, we challenged post-smolt Atlantic salmon (Salmo salar) to increasing temperatures (12 → 20°C, 1°C week–1) under normoxia or moderate hypoxia (∼70% air saturation) and compared responses in the liver after 3 days or 4 weeks at 20°C. DNA methylation was studied in six genes related to temperature stress (cirbp, serpinh1), oxidative stress (prdx6, ucp2), apoptosis (jund), and metabolism (pdk3). Here, we report that exposure to high temperature, alone or combined with hypoxia, affected the methylation of CpG sites within different genomic regulatory elements around the transcription start of these temperature/hypoxia biomarker genes. Yet, we uncovered distinct CpG methylation profiles for each treatment group, indicating that each environmental condition may induce different epigenetic signatures. These CpG methylation responses were strongly dependent on the duration of stress exposure, and we found reversible, but also persistent, CpG methylation changes after 4 weeks of exposure to 20°C. Further, several of these changes in CpG methylation correlated with transcriptional changes, and thus, can be considered as regulatory epigenetic marks (epimarkers). Our study provides insights into the dynamic associations between CpG methylation and transcript expression in Atlantic salmon, and suggests that this epigenetic mechanism may mediate physiological acclimation to short-term and long-term environmental changes.