CAENORHABDITIS-ELEGANS ORTHOLOGS OF THE ARYL-HYDROCARBON RECEPTOR ANDITS HETERODIMERIZATION PARTNER THE ARYL-HYDROCARBON RECEPTOR NUCLEAR TRANSLOCATOR

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcriptio n factor, until now described only in vertebrates, that mediates many of the carcinogenic and teratogenic effects of certain environmental p ollutants. Here, we describe orthologs of AHR and its dimerization par tner AHR nuclear translocator (ARNT) in the nematode Caenorhabditis el egans, encoded by the genes ahr-1 and aha-1, respectively. The corresp onding proteins, AHR-1 and AHA-1, share biochemical properties with th eir mammalian cognates. Specifically, AHR-1 forms a tight association with HSP90, and AHR-1 and AHA-1 interact to bind DNA fragments contain ing the mammalian xenobiotic response element with sequence specificit y. Yeast expression studies indicate that C. elegans AHR-1, like verte brate AHR, requires some form of post-translational activation. Moreov er, this requirement depends on the presence of the domains predicted to mediate binding of HSP90 and ligand. Preliminary experiments sugges t that if AHR-1 is ligand-activated, its spectrum of ligands is differ ent from that of the mammalian receptor: C. elegans AHR-1 is not photo affinity labeled by a dioxin analog, and it is not activated by beta-n aphthoflavone in the yeast system. The discovery of these genes in a s imple, genetically tractable invertebrate should allow elucidation of AHR-1 function and identification of its endogenous regulators.