Regulatory network connecting two glucose signal transduction pathways in Saccharomyces cerevisiae

Regulatory network connecting two glucose signal transduction pathways in Saccharomyces cerevisiae
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DOI:
10.1128/ec.3.1.221-231.2004
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发表时间:
2004-02-01
期刊:
影响因子:
--
通讯作者:
Johnston, M
Johnston, M
中科院分区:
其他
文献类型:
--
作者:
Kaniak, A;Xue, ZX;Johnston, M

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酿酒酵母通过多种信号转导途径感知其首选碳源葡萄糖。在一个途径中,葡萄糖通过Mig1转录抑制因子抑制许多基因的表达,该转录抑制因子由Snf1蛋白激酶调节。在另一种途径中,葡萄糖通过细胞表面的两个葡萄糖传感器诱导编码葡萄糖转运蛋白的HXT基因的表达,从而产生影响Rgt1转录因子功能的细胞内信号。我们对酵母转录组进行了分析,以确定第二条途径所针对的基因范围。通过染色质免疫沉淀检测Rgt1与其启动子的结合以及通过测量启动子LacZ融合表达的调节来验证候选靶基因。相对较少的基因可以被确认为该途径的靶点,这表明该途径主要致力于调节HXT基因的表达。在这个葡萄糖信号通路调控的基因中,有几个基因参与了葡萄糖诱导和葡萄糖抑制通路。Snf3/Rgt2-Rgt1葡萄糖诱导途径通过诱导MIG2的转录参与葡萄糖抑制,MIG2编码葡萄糖抑制基因的抑制子,并通过诱导编码Rgt1转录因子的调节因子STD1的表达来调节自身。Snf1-Mig1葡萄糖抑制途径通过抑制SNF3和MTH1的表达参与葡萄糖诱导,MTH1编码Rgt1的另一个调节因子,并通过抑制MIG1的转录进行自我调节。因此,这两个葡萄糖信号通路交织在一个调控网络中,该网络整合了这两个通路中运行的不同葡萄糖信号。
The yeast Saccharomyces cerevisiae senses glucose, its preferred carbon source, through multiple signal transduction pathways. In one pathway, glucose represses the expression of many genes through the Mig1 transcriptional repressor, which is regulated by the Snf1 protein kinase. In another pathway, glucose induces the expression of HXT genes encoding glucose transporters through two glucose sensors on the cell surface that generate an intracellular signal that affects function of the Rgt1 transcription factor. We profiled the yeast transcriptome to determine the range of genes targeted by this second pathway. Candidate target genes were verified by testing for Rgt1 binding to their promoters by chromatin immunoprecipitation and by measuring the regulation of the expression of promoter lacZ fusions. Relatively few genes could be validated as targets of this pathway, suggesting that this pathway is primarily dedicated to regulating the expression of HXT genes. Among the genes regulated by this glucose signaling pathway are several genes involved in the glucose induction and glucose repression pathways. The Snf3/Rgt2-Rgt1 glucose induction pathway contributes to glucose repression by inducing the transcription of MIG2, which encodes a repressor of glucose-repressed genes, and regulates itself by inducing the expression of STD1, which encodes a regulator of the Rgt1 transcription factor. The Snf1-Mig1 glucose repression pathway contributes to glucose induction by repressing the expression of SNF3 and MTH1, which encodes another regulator of Rgt1, and also regulates itself by repressing the transcription of MIG1. Thus, these two glucose signaling pathways are intertwined in a regulatory network that serves to integrate the different glucose signals operating in these two pathways.