Transcriptional regulation of the squalene synthase gene (ERG9) in the yeast Saccharomyces cerevisiae
Transcriptional regulation of the squalene synthase gene (ERG9) in the yeast Saccharomyces cerevisiae
复制标题
DOI：
10.1016/s0167-4781(99)00035-4
复制
发表时间：
1999-04-14
期刊：
影响因子：
--
通讯作者：
Bard, M
中科院分区：
文献类型：
--
作者：
Kennedy, MA;Barbuch, R;Bard, M
麦角甾醇生物合成途径是甲氧戊酸途径的一个特殊分支。由于细胞对类固醇的需求大于类异戊二烯，类固醇的生物合成必须独立于类异戊二烯的生物合成进行调控。在这项研究中，我们探索了角鲨烯合成酶(ERG9)在酿酒酵母中的转录调控，它是第一种专门合成甾醇的酶。进行突变搜索，以确定参与ERG9-LacZ启动子融合表达调控的基因。表型与已知的甾醇生物合成突变(ERG3、ERG7、ERG24)一致的突变体增加ERG9的表达。此外，分别针对角鲨烯合成酶和C-14甾醇去甲基酶的甾醇抑制剂扎拉戈齐酸和酮康唑处理野生型细胞也导致ERG9表达增加。数据还表明，血红素突变体增加了ERG9的表达，而厌氧条件降低了ERG9的表达。此外，血红素激活蛋白转录因子HAP1和HAP2/3/4，酵母激活蛋白转录因子YAP-1和磷脂转录因子复合体INO2/4调节ERG9的表达。在hap1、hap2/3/4和yap-1突变体中，ERG9的表达降低，而ino2/4突变体中ERG9的表达增加。本研究证明ERG9的转录受多种因素的调控，这与角鲨烯合成酶基因表达作为合成甾醇的第一步，最终合成甾醇受到高度调控的观点是一致的。(C)1999 Elsevier Science B.V.，保留所有权利。
The ergosterol biosynthetic pathway is a specific branch of the mevalonate pathway. Since the cells requirement for sterols is greater than for isoprenoids, sterol biosynthesis must be regulated independently of isoprenoid biosynthesis. In this study we explored the transcriptional regulation of squalene synthase (ERG9) in Saccharomyces cerevisiae, the first enzyme dedicated to the synthesis of sterols. A mutant search was performed to identify genes that were involved in the regulation of the expression of an ERG9-lacZ promoter fusion. Mutants with phenotypes consistent with known sterol biosynthetic mutations (ERG3, ERG7, ERG24) increased expression of ERG9. In addition, treatment of wild-type cells with the sterol inhibitors zaragozic acid and ketoconazole, which target squalene synthase and the C-14 sterol demethylase respectively, also caused an increase in ERG9 expression. The data also demonstrate that heme mutants increased ERG9 expression while anaerobic conditions decreased expression. Additionally, the heme activator protein transcription factors HAP1 and HAP2/3/4, the yeast activator protein transcription factor yAP-1, and the phospholipid transcription factor complex INO2/4 regulate ERG9 expression. ERG9 expression is decreased in hap1, hap2/3/4, and yap-1 mutants while ino2/4 mutants showed an increase in ERG9 expression. This study demonstrates that ERG9 transcription is regulated by several diverse factors, consistent with the idea that as the first step dedicated to the synthesis of sterols, squalene synthase gene expression and ultimately sterol biosynthesis is highly regulated. (C) 1999 Elsevier Science B.V, All rights reserved.