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 chimeras 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 Sp1, 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 provide new insights into the in vivo mechanism of transcriptional activation for an interesting mammalian gene.
Ko
H P
HP
Department of Molecular Pharmacology, Stanford University School of Medicine, California 94306-5332, USA.
Okino
S T
ST
Ma
Q
Q
Whitlock
J P
JP
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology; D004147:Dioxins / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D051379:Mice; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D004147:Dioxins; D018336:Receptors, Aryl Hydrocarbon; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1