Oil and hypoxia alter DNA methylation and transcription of genes related to neurological function in larval Cyprinodon variegatus

Abstract

DNA methylation is an important epigenetic mark involved in modulating transcription. While multiple studies document the ability of environmental stressors to alter methylation patterns, there is little information regarding the effects of oil and hypoxia on the methylome. Oil and hypoxic stress are threats in coastal ecosystems, which act as nursery habitats for developing fish. To explore the methylation altering effects of oil and hypoxia on developing fish, we exposed larval Cyprinodon variegatus to oil, hypoxia, or both for 48 h followed by 48 h of depuration in clean, normoxic conditions. We then used immunoprecipitation coupled with high-throughput sequencing (MeDIP seq) to evaluate genome-wide methylation changes. We also performed RNA seq to associate methylation and altered transcription. Oil and hypoxia together elicited greater impacts to methylation than either stressor individually. Additionally, the oil+hypoxia treatment exhibited an overlap between differentially methylated regions and differential gene expression at 20 loci. Functional analyses of these loci revealed enrichment of processes related to neurological function and development. Two neurological genes (slc1a2, asxl2) showed altered methylation of promoter CpG islands and transcriptional changes, suggesting epigenetic modulation of gene expression. Our results suggest a possible mechanism explaining altered behavior patterns noted in fish following oil exposure.