Genome-wide ChIP-chip analysis of the binding targets of the naïve and activated aryl hydrocarbon receptor

Knowledge of the range of genes directly regulated by the Ah receptor would facilitate integration of the complex physiologic mechanisms that regulate the response to its toxic ligands at a systems biology level. In this report, we have combined multiple technologies and knowledge-bases to conduct an integrative genome-wide analysis of Ah receptor gene targets, and interpret the results to elucidate the underlying physiological functions of the AHR in mammals. Specifically, we used chromatin immunoprecipitation and hybridization to promoter tiling arrays to map constitutive, B[a]P- and TCDD-induced Ah receptor binding sites in a mouse hepatoma cell line, incorporating gene expression data and information from predicted cis-binding elements and overlapping molecular concept signatures. Keywords: ChIP-chip; treatment response; genotype In the study presented here, mouse hepa-1c1c7 cells and c35 mutant hepa-1c1c7 derived cells with AHR unable to bind DNA, were used to predict AHR binding targets. Two biological replicates were performed each condition (the naïve state, treated with B[a]P, and treated with TCDD). Four replicate chips were performed for non-specific IgG.