POTENT TRANSACTIVATION DOMAINS OF THE AH RECEPTOR AND THE AH RECEPTORNUCLEAR TRANSLOCATOR MAP TO THEIR CARBOXYL TERMINI

The Ah receptor (AHR) is a ligand-activated transcription factor that is structurally related to its dimerization partner, the Ah receptor n uclear translocator (ARNT), and two Drosophila proteins, SIM and PER. Ah four proteins contain a region of homology now referred to as a PAS homology domain. In addition, the AHR, ARNT, and SIM harbor a basic r egion helix-loop-helix motif in their N termini, whereas PER does not. Previous mapping studies of the AHR have demonstrated that the PAS do main contains sequences required for ligand recognition, dimerization, and interaction with the 90-kDa heat shock protein. They also have co nfirmed that the basic region helix-loop-helix domain plays a role in both dimerization and sequence-specific DNA binding. To identify domai ns involved in transactivation of target genes, we generated chimeras of AHR/ARNT deletion mutants with the DNA binding region of the yeast Gal4 protein, transiently expressed these in COS-l cells, and monitore d their capacity to activate the chloramphenicol acetyltransferase rep orter gene under the control of a minimal promoter driven by enhancer elements recognized by Gal4. Extensive analysis of these fusions revea led that the AHR and ARNT harbor potent transactivation domains within their C termini. Importantly, the amino-terminal halves of both the A HR and ARNT were found to be devoid of transactivation activity.