Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
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DOI：
10.1093/emboj/cdf415
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发表时间：
2002-08-01
期刊：
影响因子：
11.4
通讯作者：
Winston, F
中科院分区：
文献类型：
--
作者：
Hongay, C;Jia, N;Winston, F
酿酒酵母 MOT3 基因编码一种参与转录抑制和激活的核蛋白。然而，mot3Delta 突变在正常生长条件下仅引起轻微的表型。为了了解有关 Mot3 功能的更多信息，我们进行了合成致死筛选。该筛选鉴定了 PAN1（正常内吞作用所需的基因）和 VPS41（液泡融合和蛋白质靶向所需的基因），表明 Mot3 在膜相关基因的调节中发挥作用。转录分析表明，在有氧和缺氧生长过程中，Mot3 都会抑制 ERG2、ERG6 和 ERG9（麦角甾醇生物合成所需的基因）的转录。染色质免疫沉淀实验表明这种抑制是直接的。麦角甾醇已被证明是内吞作用和同型液泡融合所必需的，从而提供了 Mot3 和这些过程之间的联系。与这些结果一致，mot3Delta 突变体具有许多相关缺陷，包括同型液泡融合受损和甾醇水平增加。综上所述，我们的数据表明，Mot3 对麦角甾醇生物合成基因的正确转录调节对于正常液泡功能很重要，并且可能对于内吞膜转运系统也很重要。
The Saccharomyces cerevisiae MOT3 gene encodes a nuclear protein implicated in both repression and activation of transcription. However, a mot3Delta mutation causes only mild phenotypes under normal growth conditions. To learn more about Mot3 function, we have performed a synthetic lethal screen. This screen identified PAN1, a gene required for normal endocytosis, and VPS41, a gene required for vacuolar fusion and protein targeting, suggesting a role for Mot3 in the regulation of membrane-related genes. Transcriptional analyses show that Mot3 represses transcription of ERG2, ERG6 and ERG9, genes required for ergosterol biosynthesis, during both aerobic and hypoxic growth. Chromatin immunoprecipitation experiments suggest that this repression is direct. Ergosterol has been shown to be required for endocytosis and homotypic vacuole fusion, providing a link between Mot3 and these processes. Consistent with these results, mot3Delta mutants have a number of related defects, including impaired homotypic vacuole fusion and increased sterol levels. Taken together, our data suggest that proper transcriptional regulation of ergosterol biosynthetic genes by Mot3 is important for normal vacuolar function and probably for the endocytic membrane transport system.