Dioxin-inducible transactivation in a chromosomal setting - Analysis of the acidic domain of the Ah receptor

We analyzed the transactivation function of the acidic segment of the Ah re ceptor (amino acids 515-583) by reconstituting AhR-defective mouse hepatoma cells with mutants. Our data reveal that both hydrophobic and acidic resid ues are important for transactivation and that these residues are clustered in two regions of the acidic segment of AhR. Both regions are crucial for function, because disruption of either one substantially impairs transactiv ation of the chromosomal CYP1A1 target gene. Neither region contains an ami no acid motif that resembles those reported for other acidic activation dom ains. Furthermore, proline substitutions in both regions do not impair tran sactivation in vivo, a finding that implies that cu-helix formation is not required for function.