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首页> 外文期刊>Molecular and Cellular Biology >Coupling Phosphate Homeostasis to Cell Cycle-Specific Transcription: Mitotic Activation of Saccharomyces cerevisiae PHO5 by Mcm1 and Forkhead Proteins
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Coupling Phosphate Homeostasis to Cell Cycle-Specific Transcription: Mitotic Activation of Saccharomyces cerevisiae PHO5 by Mcm1 and Forkhead Proteins

机译：磷酸稳态与细胞周期特定转录的耦合：Mcm1和叉头蛋白的酿酒酵母PHO5的有丝分裂活化。

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Cells devote considerable resources to nutrient homeostasis, involving nutrient surveillance, acquisition, and storage at physiologically relevant concentrations. Many Saccharomyces cerevisiae transcripts coding for proteins with nutrient uptake functions exhibit peak periodic accumulation during M phase, indicating that an important aspect of nutrient homeostasis involves transcriptional regulation. Inorganic phosphate is a central macronutrient that we have previously shown oscillates inversely with mitotic activation of PHO5. The mechanism of this periodic cell cycle expression remains unknown. To date, only two sequence-specific activators, Pho4 and Pho2, were known to induce PHO5 transcription. We provide here evidence that Mcm1, a MADS-box protein, is essential for PHO5 mitotic activation. In addition, we found that cells simultaneously lacking the forkhead proteins, Fkh1 and Fkh2, exhibited a 2.5-fold decrease in PHO5 expression. The Mcm1-Fkh2 complex, first shown to transactivate genes within the CLB2 cluster that drive G2/M progression, also associated directly at the PHO5 promoter in a cell cycle-dependent manner in chromatin immunoprecipitation assays. Sds3, a component specific to the Rpd3L histone deacetylase complex, was also recruited to PHO5 in G1. These findings provide (i) further mechanistic insight into PHO5 mitotic activation, (ii) demonstrate that Mcm1-Fkh2 can function combinatorially with other activators to yield late M/G1 induction, and (iii) couple the mitotic cell cycle progression machinery to cellular phosphate homeostasis.
机译：细胞将大量资源用于营养稳态，包括以生理相关浓度监视营养，获取和储存营养。许多编码具有营养吸收功能蛋白的啤酒酵母转录物在M期表现出周期性的峰值积累，表明营养稳态的重要方面涉及转录调控。无机磷酸盐是一种主要的常量营养素，我们之前已经证明它与 PHO5 的有丝分裂激活呈相反的振荡。这种周期性细胞周期表达的机制仍然未知。迄今为止，已知只有两种序列特异性激活剂Pho4和Pho2可以诱导 PHO5 转录。我们在这里提供的证据表明，MADS-box蛋白Mcm1对于 PHO5 有丝分裂激活至关重要。此外，我们发现同时缺乏叉头蛋白Fkh1和Fkh2的细胞在 PHO5 表达中降低了2.5倍。 Mcm1-Fkh2复合物，首先显示出可激活CLB2簇中驱动G 2 / M进展的基因，也直接与 PHO5 启动子相关，且依赖细胞周期染色质免疫沉淀试验的方法Sds3是Rpd3L组蛋白脱乙酰基酶复合物的特异性成分，也被募集到G 1 中的 PHO5 中。这些发现提供了（i）对 PHO5 有丝分裂激活的进一步机理研究，（ii）表明Mcm1-Fkh2可以与其他激活剂组合发挥功能，以产生晚期M / G 1 诱导。和（iii）将有丝分裂细胞周期进程机制与细胞磷酸盐动态平衡耦合。

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