CONSTITUTIVE FUNCTION OF THE BASIC HELIX-LOOP-HELIX PAS FACTOR ARNT -REGULATION OF TARGET PROMOTERS VIA THE E-BOX MOTIF

Arnt is a nuclear basic helix-loop-helix (bHLH) transcription factor t hat, contiguous with the bHLH motif, contains a region of homology (PA S) with the Drosophila factors Per and Sim. Arnt dimerizes in a ligand -dependent manner with the bHLH dioxin receptor, a process that enable s the in-(2,3,7,8-tetrachlorodibenzo-p-dioxin)-activated Arnt-dioxin r eceptor complex to recognize dioxin response elements of target promot ers. In the absence of dioxin, Arnt does not bind to this target seque nce motif. The constitutive function of Arnt is presently not understo od. Here we demonstrate that Arnt constitutively bound the E box motif CACGTG that is also recognized by a number of distinct bHLH factors, including USF and Max. Importantly, amino acids that have been identif ied to be critical for E box recognition by Max and USF are conserved in Arnt. Consistent with these observations, full-length Arnt, but not an Arnt deletion mutant lacking its potent C-terminal transactivation domain, constitutively activated CACGTG E box-driven reporter genes i n vivo. These results indicate a role of Arnt in regulation of a netwo rk of target genes that is distinct from that regulated by the Arnt-di oxin receptor complex in dioxin-stimulated cells.