Two aryl hydrocarbon receptors (rtAHR2␣ and rtAHR2␤) have been identified in the rainbow trout (Oncorhynchus mykiss). These receptors share 98% amino acid identity, yet their functional properties differ. Both rtAHR2␣ and rtAHR2␤ bind 2,3,7,8-tetrachlorodibenzop-dioxin (TCDD), dimerize with rainbow trout ARNTb (rtARNTb), and recognize dioxin response elements in vitro. However, in a transient transfection assay the two proteins show differential ability to recognize enhancers, produce

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... ation, and respond to TCDD. To identify the sequence differences that confer the functional differences between rtAHR2␣ and rtAHR2␤, we constructed chimeric rtAHRs, in which segments of one receptor form was replaced with the corresponding part from the other isoform. This approach progressively narrowed the region being examined to a single residue, corresponding to position 111 in rtAHR2␤. Altering this residue in rtAHR2␤ from the lysine to glutamate found in rtAHR2␣ produced an rtAHR2␤ with the properties of rtAHR2␣. All other known AHRs resemble rtAHR2␣ and carry glutamate at this position, located at the N terminus of the PAS-A domain. We tested the effect of altering this glutamate in the human and zebrafish AHRs to lysine. This lysine substitution produced AHRs with transactivation properties that were similar to rtAHR2␤. These results identify a critical residue in AHR proteins that has an important impact on transactivation, enhancer site recognition, and regulation by ligand.