A novel sequence element is involved in the transcriptional regulation of expression of the ERG1 (squalene epoxidase) gene in Saccharomyces cerevisiae.

作者: Regina Leber , Rainer Zenz , Klarissa Schröttner , Sandra Fuchsbichler , Brigitte Pühringer

DOI: 10.1046/J.1432-1327.2001.01940.X

关键词:

摘要: Squalene epoxidase is an essential enzyme in the ergosterol-biosynthesis pathway. It catalyzes epoxidation of squalene to 2,3-oxidosqualene and specific target antifungal drug terbinafine. Treatment yeast cells with this inhibitor leads accumulation sterol depletion. As ergosterol fulfils several functions, each requiring optimal concentrations, synthesis sterols must be tightly regulated. This study focuses on sterol-mediated regulation expression ERG1 gene, which codes for Saccharomyces cerevisiae. Inhibition biosynthesis terbinafine increases a concentration-dependent manner maximum sevenfold. later steps ergosterol-biosynthetic pathway by ketoconazole, lanosterol-14alpha-demethylase, U18666A, squalene-2,3-epoxide-lanosterol cyclase, also induce ERG1, suggesting that positively regulated diminished intracellular levels. The regulatory effect manifested at level transcription. Deletion analysis promoter identified novel DNA sequence element. Two 6-bp direct repeats, separated 4 bp, AGCTCGGCCGAGCTCG, are unique promoter. A fragment containing region confers ergosterol-regulated otherwise unregulated CYC1 construction. One copy element, AGCTCG, sufficient confer regulation, albeit less effectively than when both elements present, whereas removal from loss sterol-dependent regulation.

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