Zebrafish (Danio rerio) ecotoxicological ABCB4, ABCC1 and ABCG2a gene promoters depict spatiotemporal xenobiotic multidrug resistance properties against environmental pollutants

Abstract

Marine organisms are naturally equipped with multixenobiotic resistance mechanisms that are often governed by ATP-binding cassette (ABC) transporter family members. Previous studies focused on the target genes of ABC but little is known about the functionality of their promoter regions. Due to the importance of promoters in ABC transporter gene regulation, we functionally characterized three major xenobiotic transporter promoters of zebrafish, namely ABCB4, ABCC1 and ABCG2a via in silico transcription factor binding analysis and in vivo spatiotemporal expression analysis. The former revealed the major functional contributors (such as AP-1, C/EBP beta, HNF-1 and NF-1 TFBSs) towards promoter activity enhancement across four different tissues (liver, muscle, cell cycle and immune cells) where majority of them discovered were liver-specific whereas the latter unearthed the localization of these promoters at liver and intestinal tracts during late embryogenesis (48, 72 and 96 hpf). This study contributes towards future xenobiotic transporter ecotoxicology studies in zebrafish.