cAMP-dependent transcription of the human CYP21B (P-450C21) gene requires a cis-regulatory element distinct from the consensus cAMP-regulatory element.

作者: N Kagawa , M R Waterman

DOI: 10.1016/S0021-9258(19)38591-6

关键词: Sp3 transcription factorE-boxEnhancerBiologyGATA6PromoterTranscription factorMolecular biologyResponse elementReporter gene

摘要: By utilizing chimeric genes constructed from 5'-flanking sequences of the human CYP21B (P-450C21) gene and reporter (chloramphenicol acetyltransferase or rabbit beta-globin), a 34-nucleotide sequence has been found to be required for cAMP-dependent transcription. This (-129/-96 base pairs) shows no homology that consensus (CRE) cAMP-regulatory element. Gel retardation analysis protein-DNA complex is formed between this DNA nuclear proteins mouse adrenal Y1 tumor cells bovine cortical fetal tissue formation cannot competed by containing CRE sequence. Even though cAMP-enhanced accumulation P-450C21 mRNA in primary cultures adrenocortical inhibited protein synthesis inhibitor, cycloheximide, transcription enhanced cAMP-responsive -129/-96-base pair fragment not. We conclude (CYP21B), an event maintenance optimal steroidogenic capacity cortex, involves stable factor(s) distinct CRE-binding protein. Furthermore cis-regulatory element those associated with other steroid hydroxylase genes, 17 alpha-hydroxylase cytochrome P-450, cholesterol side chain cleavage 11 beta-hydroxylase suggesting each these may require its own set specific factors regulation.

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