Abstract

The aryl hydrocarbon receptor, a ligand-activated transcription factor, regulates the responses to toxic polycyclic and halogenated aromatic compounds in vertebrates.  When activated by xenobiotic ligands, the receptor induces the transcription of detoxification genes and modulates cell cycle signaling pathways that run in combinatorial interaction with the detoxification pathways.  We have integrated information from chromatin binding, expression profiling, binding sequence motif analysis and prior molecular concepts to identify receptor regulatory targets in all known gene promoters of the mouse genome.  Unexpectedly, the naïve receptor in unstimulated cells targets an extensive array of gene clusters involved in regulation of gene expression, differentiation and pattern specification, cross-linking multiple morphogenesis and developmental programs.  Activation by ligand extends binding characteristics to include sites in the promoters of xenobiotic metabolism genes.  The vertebrate receptor appears to possess previously unsuspected regulatory functions that are potential targets of environmental injury during development.

Supplementary Materials