Oct-1 transcription factor is a negative regulator of rat CYP1A1 expression via an octamer sequence in its negative regulatory element.

Publisher: American Society for Pharmacology and Experimental Therapeutics Country of Publication: United States NLM ID: 0035623 Publication Model: Print Cited Medium: Print ISSN: 0026-895X (Print) Linking ISSN: 0026895X NLM ISO Abbreviation: Mol Pharmacol Subsets: MEDLINE

Original Publication: Bethesda, MD : American Society for Pharmacology and Experimental Therapeutics

DNA-Binding Proteins* ; Gene Expression Regulation, Enzymologic* ; Regulatory Sequences, Nucleic Acid*; Cytochrome P-450 Enzyme System/*biosynthesis ; Cytochrome P-450 Enzyme System/*genetics ; Homeodomain Proteins/*metabolism ; Transcription Factors/*metabolism; Animals ; Base Sequence ; Binding Sites ; Carcinoma, Hepatocellular ; Cell Line ; Cell Nucleus/metabolism ; Homeodomain Proteins/biosynthesis ; Host Cell Factor C1 ; Humans ; Kinetics ; Liver Neoplasms ; Luciferases/biosynthesis ; Luciferases/metabolism ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Octamer Transcription Factor-1 ; Oligodeoxyribonucleotides ; Point Mutation ; Promoter Regions, Genetic ; Rats ; Recombinant Proteins/biosynthesis ; Recombinant Proteins/metabolism ; Transcription Factors/biosynthesis ; Transfection

The rat CYP1A1 negative regulatory element (NRE) contains AP-1 and Oct-1 motifs at -808 to -788 bp. The CYP1A1 sequence from -813 to -779 bp and an identical sequence bearing a point mutation in the octamer motif were synthesized. Gel mobility shift assays showed the formation of two complexes with the wild-type CYP1A1 sequence and nuclear extracts from H4IIE and HepG2 hepatoma cells and from rat liver. The formation of the major complex was significantly reduced with the mutant octamer-containing oligomer and was specifically competed by an Oct-1 oligodeoxyribonucleotide. The addition of Oct-1 antibody caused a supershift of the major complex. The presence of the wild-type sequence, but not the mutant octamer sequence, caused a 3-fold decrease in SV40 enhancerless promoter activity in transfected HepG2 cells. Co-transfection of an Oct-1 expression vector with rat CYP1A1 NRE octamer-containing, promoter/reporter gene constructs specifically further decreased promoter activity of the wild-type octamer-containing constructs in HepG2 cells. The results indicate that Oct-1 binds to the rat CYP1A1 promoter NRE and is a negative regulator of rat CYP1A1 expression.

CA36106 United States CA NCI NIH HHS; ES03980 United States ES NIEHS NIH HHS

0 (DNA-Binding Proteins)
0 (HCFC1 protein, human)
0 (Homeodomain Proteins)
0 (Host Cell Factor C1)
0 (Octamer Transcription Factor-1)
0 (Oligodeoxyribonucleotides)
0 (POU2F1 protein, human)
0 (Pou2f1 protein, rat)
0 (Recombinant Proteins)
0 (Transcription Factors)
9035-51-2 (Cytochrome P-450 Enzyme System)
EC 1.13.12.- (Luciferases)

Date Created: 19960201 Date Completed: 19960703 Latest Revision: 20081121

20231215

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