Regulating resistance: CncC:Maf, antioxidant response elements and the overexpression of detoxification genes in insecticide resistance

Although genetic and genomic tools have greatly furthered our understanding of resistance-associated mutations in molecular target sites of insecticides, the genomic basis of transcriptional regulation of detoxification loci in insect pests and vectors remains relatively unexplored. Recent work using RNAi, reporter assays and comparative genomics are beginning to reveal the molecular architecture of this response, identifying critical transcription factors and their binding sites. Central to this is the insect ortholog of the mammalian transcription factor Nrf2, Cap 'n' Collar isoform-C (CncC) which as a heterodimer with Maf-S regulates the transcription of phase I, II and III detoxification loci in a range of insects, with CncC knockdown or upregulation directly affecting phenotypic resistance. CncC:Maf binds to specific antioxidant response element sequences upstream of detoxification genes to initiate transcription. Recent work is now identifying these binding sites for resistance-associated loci and, coupled with genome sequence data and reporter assays, enabling identification of polymorphisms in the CncC:Maf binding site which regulate the insecticide resistance phenotype.