DNA Methylation Dynamics in Atlantic Salmon (Salmo salar) after being Challenged with High Temperature and Moderate Hypoxia

Plant and Animal Genome XXVII Conference (PAG XXVIII), 11-15 January 2020, San Diegohe marine environment is predicted to become warmer and more hypoxic over this century, and these conditions may become a challenge for cultured Atlantic salmon by negatively affecting their growth, immunology and welfare. DNA methylation mediates phenotypically plastic responses in gene expression that can potentially facilitate acclimatization responses. Thus, we measured DNA methylation from salmon that were subjected to: i) control conditions (normoxia, 12°C); ii) an incremental increase in temperature (12°C to 20°C, at 1°C per week) and then held at 20°C for 4 weeks; or iii) the former temperature regimen in combination with moderate hypoxia (~70% air saturation). DNA methylation levels were measured at CpG sites within a ~500 bp region (Promotor, 5’UTR, Exon, Intron) of six important liver biomarker genes (cribp, jund, pkd3, prdx6, serpinh1, and ucp2). Considering both experimental groups, we found 12 CpGs (out of 94 total) across the six genes that were differentially methylated when exposed to 20°C for 3 days, whereas only 6 CpGs from three genes (jund, prdx6 and ucp2) were affected after 4 weeks at 20°C. At both time points, we uncovered distinct DNA methylation profiles for fish of each treatment group, suggesting that high temperature and moderate hypoxia were inducing different CpG methylation changes in the liver of salmon. Further, we report significant relationships between CpG methylation and the mRNA expression of these genes that are complex and dynamic. These changes in DNA methylation may be an important regulatory mechanism allowing Atlantic salmon to quickly respond to new environmental challenges associated with global warmingThis research was funded by the Ocean Frontier Institute, through the Canada First Research Excellence Fun

DNA Methylation Dynamics in Atlantic Salmon (Salmo salar) Challenged With High Temperature and Moderate Hypoxia

26 pages, 7 figures, 2 tables, supplementary material https://doi.org/10.3389/fmars.2020.604878.-- Data Availability Statement: The datasets generated for this study can be found in the online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/geo/, GSE153343; doi: 10.1594/PANGAEA.913696The 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 changesFunding for this research was provided to AKG by the Ocean Frontier Institute, through an award from the Canada First Research Excellence Fund (20181007) and was supported by the Spanish Ministry of Science Grants AGL2015-73864-JIN “Ambisex” and RYC2018-024017-I, and an “Interomics” Grant (202030E004) from the Spanish National Research Council (CSIC) to LR. This research was conducted on samples collected through the “Mitigating the Impact of Climate-Related Challenges on Salmon Aquaculture (MICCSA)” project. MICCSA funding was provided by the Atlantic Canada Opportunities Agency (781-9658-205222), Innovate NL (5404-1209-104), and Innovate PEI to AKGWith the funding support of the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2019-000928-S), of the Spanish Research Agency (AEI)Peer reviewe

Transcriptional and DNA methylation responses in Atlantic salmon (Salmo Salar) when challenged with increasing temperature and moderate hypoxia

Functional annotation of the Atlantic salmon genome, translation to improved health and performance in Aquaculture, 26-27 August 2019, Canad