TRANSACTIVATION DOMAINS FACILITATE PROMOTER OCCUPANCY FOR THE DIOXIN-INDUCIBLE CYP1A1 GENE IN-VIVO

We have studied the transcriptional regulation of the dioxin-inducible mouse CYP1A1 gene in its native chromosomal setting. We analyzed the ability of aromatic hydrocarbon receptor (AhR) mutants and AhR chimera s to restore dioxin responsiveness to the CYP1A1 gene in AhR-defective mouse hepatoma cells. Our data reveal that transactivation domains in AhR's C-terminal half mediate occupancy of the nuclear factor 1 site and TATA box for the CYP1A1 promoter in vivo. Transactivation domains of VP16 and AhR nuclear translocator, but not Spl, can substitute for AhR's C-terminal half in facilitating protein binding at the promoter, Our data also reveal an apparent linear relationship between promoter occupancy and CYP1A1 gene expression in chromatin. These findings pro vide new insights irate the in vivo mechanism of transcriptional activ ation for an interesting mammalian gene.