A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae
A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.106.059964
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发表时间：
2006-09-01
期刊：
影响因子：
3.3
通讯作者：
Rine, Jasper
中科院分区：
文献类型：
--
作者：
Davies, Brandon S. J.;Rine, Jasper
Upc 2 p和Ecm 22 p是一对转录因子，负责酵母中麦角甾醇生物合成酶编码基因（ERG基因）的基础和诱导表达。upc 2 p作为低氧表达基因的调节剂发挥第二个作用。固醇和血红素都依赖于分子氧来合成，因此两者的水平都有可能作为细胞氧环境的指标。Hap 1 p是一种血红素依赖性转录因子，Upc 2和Ecm 22 p都依赖于ERG基因的基础水平表达。然而，诱导ERG基因和缺氧表达的DAN/ TIR基因Upc 2 p和Ecm 22 p发生在响应甾醇耗竭，而不是血红素耗竭。事实上，在甾醇耗尽后，Upc 2 p不再需要Hap 1 p来激活ERG基因。Mot 3 p是一种广泛作用的抑制/激活蛋白，以前被证明可以抑制ERG基因的表达，但其机制尚不清楚。我们建立了Mot 3 p直接结合到Ecm 22 p和抑制Ecm 22 p-但不是Upc 2 p-介导的基因诱导。
Upc2p and Ecm22p are a pair of transcription factors responsible for the basal and induced expression of genes encoding enzymes of ergosterol biosynthesis in yeast (ERG genes). Upc2p plays a second role as a regulator of hypoxically expressed genes. Both sterols and heme depend upon molecular oxygen for their synthesis, and thus the levels of both have the potential to act as indicators of the oxygen environment of cells. Hap1p is a heme-dependent transcription factor that both Upc2 and Ecm22p depend upon for basal level expression of ERG genes. However, induction of both ERG genes and the hypoxically expressed DAN/ TIR genes by Upc2p and Ecm22p occurred in response to sterol depletion rather than to heme depletion. Indeed, upon sterol depletion, Upc2p no longer required Hap1p to activate ERG genes. Mot3p, a broadly acting repressor/activator protein, was previously shown to repress ERG gene expression, but the mechanism was unclear. We established that Mot3p bound directly to Ecm22p and repressed Ecm22p- but not Upc2p-mediated gene induction.