Differential DNA methylation following developmental exposure to triclosan (TCS) in 7dpf zebrafish larvae
ABSTRACT: There is increasing evidences that toxicant exposure can alter methylation profiles, particularly during embryogenesis when DNA methylation patterns are established. In order to investigate the effects of TCS on DNA methylation and its consequences on gene expression during embryogenesis, we exposed zebrafish eggs during 7 days post fertilisation (dpf) to 50 and 100 µg/L of TCS. Although, global DNA methylation was not affected by TCS exposure, a total of 171 differentially methylated fragments (DMFs) between conditions were identified. The majority of the DMFs were found between the two exposed groups, reflecting distinct triggered responses. Gene ontology analysis revealed that pathways involved in TGF-beta signaling were enriched in larvae exposed to 50 µg/L, while de novo pyrimidine biosynthesis functions were overrepresented in fish exposed to 100 µg/L of TCS. In parallel, gene expression analysis revealed a positive correlation between DNA methylation patterns and gene expression levels for introns, together with significant alterations of the transcription of genes involved in nervous system development, transcriptional factors and histone methyltransferase. Overall our work provides evidence that TCS impacts DNA methylation during zebrafish early embryogenesis and brings clues about the toxicity mechanisms of TCS during this critical period of development. Overall design: Collected eggs were distributed individually in 24-well microplates, each well containing 2 mL of test solutions. 6 plates were used per conditions (control, exposed to 50 µg/L and exposed to 100 µg/L of TCS) for RRBS analysis. At the end of the 7 days of exposition, 6 pools of 24 larvae were sampled and only 4 were used for RRBS librairies.