Integrative analysis of transcriptional and DNA methylation changes associated with PCB126 exposure in adult zebrafish (Danio rerio)

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor well known for mediating the toxicity of environmental chemicals such as polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs). There is extensive knowledge on the range of target genes regulated by AHR ligands. However, there is limited information on the effect of AHR ligands on DNA methylation. The objective of this study is to investigate genome-wide changes in DNA methylation and gene expression patterns in response to PCB126 exposure. Adult zebrafish were exposed to 10 nM PCB126 for 24 hours (waterborne exposure) and were reared in clean water for 7 days before tissue sampling. DNA methylation and transcriptional changes in the liver and brain tissues were quantified by Reduced Representation Bisulfite Sequencing (RRBS) and RNAseq, respectively. RRBS analysis revealed DNA hypomethylation in response to PCB exposure in both liver and brain tissues. We observed 482 and 476 differentially methylated regions (DMRs) in the liver and brain tissues respectively. Most of the DMRs are located more than 20 kilobases upstream of the transcriptional start sites. RNAseq results from the liver revealed differential expression of genes related to xenobiotic metabolism, oxidative stress and carbohydrate metabolism in response to PCB exposure. In the brain, PCB exposure altered the expression of genes involved in myelination and glutamate signaling. Our results suggest that there is very little correlation between DNA methylation and gene expression patterns among the differentially expressed genes (DEGs). We are currently investigating the relationship between DMRs and DEGs. Overall design: Two different tissues (Liver and brain) from PCB126 and DMSO-exposed zebrafish were analyzed for DNA methylation and gene expression using RRBS and RNAseq respectively. Four biological replicates per treatment were analyzed (n=4 individual fish).

16

Aluru N, Karchner SI, Krick KS, Zhu W, Liu J