Competitive inhibition of the transcription of rabbit CYP1A1 gene by upstream stimulatory factor 1 (USF1).
The induction of CYP1A1 by 3-methylcholanthrene occurs in neonatal but not in adult rabbits. The expression of aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (Arnt) mRNAs is seen even in adult rabbits. The CYP1A1 inducibility does not seem to be regulated by DNA methylation, known to inhibit the transcription of a gene(s). Preliminary experiments suggest that a constitutive factor(s) in adult liver nuclear extracts is bound to the core sequence of rabbit xenobiotic-responsive element (XRE). The sequence of rabbit XRE overlaps with that of the upstream stimulatory factor 1 (USF1)-binding site. The AhR/Arnt-mediated activation of XRE-TK/Luc reporter gene in RK13 cells is blocked by transfection with a USF1 expression vector. These results indicate that the XRE of the rabbit CYP1A1 gene is recognized by the basic helix-loop-helix proteins to regulate the expression of CYP1A1 in both an agonistic (AhR/Arnt) and an antagonistic (USF1) manner.
Laboratory of Drug Metabolism, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Y
Y
Takahashi
T
T
Kamataki
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001665:Binding Sites; D001667:Binding, Competitive; D019363:Cytochrome P-450 CYP1A1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D004268:DNA-Binding Proteins; D004790:Enzyme Induction; D011817:Rabbits; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism / Q000502:physiology; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology; D014162:Transfection; D051720:Upstream Stimulatory Factors
D004268:DNA-Binding Proteins; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051720:Upstream Stimulatory Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D019363:Cytochrome P-450 CYP1A1