Regulatory mechanisms of cAMP-dependent and cell-specific expression of human steroidogenic cytochrome P450scc (CYP11A1) gene.
Cytochrome P450scc (CYP11A1) is the enzyme that catalyzes the side-chain cleavage reaction of cholesterol, the first and rate-limiting reaction in the biosynthesis of steroid hormones in the adrenal cortex. DNase-I-footprinting analysis using nuclear extracts from the bovine adrenal cortex and the 5' upstream regulatory region (nucleotides -1697 to -1523) of the CYP11A1 gene, which is mainly required for response to cAMP [Inoue, H., Watanabe, N., Higashi, Y. & Fujii-Kuriyama, Y. (1991) Eur. J. Biochem. 195, 563-569], revealed that some protein factors bound to that region. One of the sequences protected by the binding factors is a cAMP-responsive-element (CRE)-like sequence, which is known to be recognized by CRE-binding protein (CREB) or its related proteins, and another is a sequence designated Ad4 which is bound by a tissue-specific factor, Ad4-binding protein (Ad4BP). The region containing the two closely arranged DNA sequences showed a high level of cAMP responsive and cell-specific expression when it was fused to the basal promoters. Introduction of point mutations in these sequences demonstrated that the CREB/ATF factors and Ad4BP bound to the sequences showed synergistic enhancer effects on cAMP-responsive and cell-specific expression of the CYP11A1 gene.
Department of Chemistry, Faculty of Science, Tohoku University, Sendai, Japan.
N
N
Watanabe
H
H
Inoue
Y
Y
Fujii-Kuriyama
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002417:Cattle; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D000242:Cyclic AMP / Q000494:pharmacology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004742:Enhancer Elements, Genetic; D051717:Fushi Tarazu Transcription Factors; D015971:Gene Expression Regulation, Enzymologic; D018398:Homeodomain Proteins; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010957:Plasmids; D017354:Point Mutation; D018160:Receptors, Cytoplasmic and Nuclear; D012045:Regulatory Sequences, Nucleic Acid; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D015345:Oligonucleotide Probes; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; D000242:Cyclic AMP; D002786:Cholesterol Side-Chain Cleavage Enzyme; D003850:Deoxyribonuclease I