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首页> 外文期刊>Molecular and Cellular Biology >Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor
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Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor

机译：血红素水平在转录激活因子和转录抑制因子之间切换酿酒酵母Hap1的功能。

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摘要

Changes in oxygen levels cause widespread changes in gene expression in organisms ranging from bacteria to humans. In Saccharomyces cerevisiae, this response is mediated in part by Hap1, originally identified as a heme-dependent transcriptional activator that functions during aerobic growth. We show here that Hap1 also plays a significant and direct role under hypoxic conditions, not as an activator, but as a repressor. The repressive activity of Hap1 controls several genes, including three ERG genes required for ergosterol biosynthesis. Chromatin immunoprecipitation experiments showed that Hap1 binds to the ERG gene promoters, while additional experiments showed that the corepressor Tup1/Ssn6 is recruited by Hap1 and is also required for repression. Furthermore, mutational analysis demonstrated that conserved Hap1 binding sites in the ERG5 5′ regulatory region are required for repression. The switch of Hap1 from acting as a hypoxic repressor to an aerobic activator is determined by heme, which is synthesized only in the presence of oxygen. The ability of Hap1 to function as a ligand-dependent repressor and activator is a property shared with mammalian nuclear hormone receptors and likely allows greater transcriptional control by Hap1 in response to changing oxygen levels.
机译：氧气含量的变化会导致从细菌到人类等生物体内基因表达的广泛变化。在酿酒酵母中，这种反应部分由Hap1介导，Hap1最初被鉴定为在有氧生长过程中发挥功能的血红素依赖性转录激活因子。我们在这里表明，Hap1在缺氧条件下也起着重要而直接的作用，不是作为激活物，而是作为阻遏物。 Hap1的抑制活性控制几个基因，包括麦角固醇生物合成所需的三个 ERG 基因。染色质免疫沉淀实验表明Hap1与 ERG 基因启动子结合，而另外的实验表明Hap1募集了核心抑制剂Tup1 / Ssn6，并且其也是抑制的必需条件。此外，突变分析表明， ERG5 5'调控区域中保守的Hap1结合位点是抑制所必需的。 Hap1从充当低氧阻遏物到有氧激活物的转换由血红素决定，血红素仅在氧气存在下合成。 Hap1充当配体依赖性阻遏物和激活剂的能力是哺乳动物核激素受体共有的特性，并且可能允许Hap1响应于不断变化的氧气水平进行更大的转录控制。

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