Regulation of nitrogen catabolic gene expression

氮分解代谢基因表达的调节

• 批准号: 6625605
• 负责人: TERRANCE G. COOPER
• 金额: $ 31.21万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-02-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625605
• 关键词: Saccharomyces cerevisiae; binding sites; fungal genetics; gene expression; gene mutation; genetic mapping; nitrogen metabolism; phosphorylation; protein kinase; protein localization; regulatory gene; transcription factor

DESCRIPTION (provided by applicant): Nitrogen metabolism in the yeast S. cerevisiae is an excellent model system in which to study eucaryotic transcriptional regulation and regulatory networks. This yeast is able to selectively utilize good nitrogen sources in preference to poor ones. This selectivity (designated nitrogen catabolite repression, NCR) is accomplished through regulated operation of four GATA-transcription factors (Gln3p, Gat1p/Nil1p, Dal80p/Uga43p, Deh1p/ GZF3p) that bind to GATA-containing sequences in the promoters of NCR-sensitive genes. Aggregate work from several laboratories, including our own, has shown that when nitrogen is in excess, Gln3p and Gat1p are phosphorylated and excluded from the nucleus. When nitrogen is limiting, these proteins are no longer phosphorylated, become localized to the nucleus, and mediate NCR-sensitive transcription. We propose to continue our studies of the GATA-family regulon, performing experiments that will elucidate the steps and proteins involved in the regulation of Gln3p, Gat1p and Ure2p activities and intracellular localization. We will also investigate the mechanisms by which Mks1p influences operation of the GATA regulon. We have established genome-wide transcription analysis in our lab and propose to identify: new members of the GATA-factor regulon, the ways in which the member genes are regulated, and how they in turn regulate GATA-factor gene expression and activity. Three new GATA-factors, Gat2p, Gat3p and Gat4p, were discovered in our pilot experiment. We propose to identify the functions of Gat2p, which is the GATA-factor most structurally homologous to Gat1p. We will also determine how Gat2p itself is regulated. We are especially interested in the interface between and integration of GATA-factor regulon components with other regulatory systems in the cell. The complexity of even this simple system is daunting, but will yield highly useful information and experience for developing and interpreting studies of far more complicated yeast and mammalian regulatory cascades.

描述（由申请人提供）： 酵母的氮代谢。酿酒酵母是一个很好的模型系统， 研究真核生物的转录调控和调控网络。 该酵母能够选择性地优先利用好的氮源 给穷人这种选择性（称为氮分解代谢物抑制，NCR） 是通过四个GATA转录因子的调控操作完成的 （Gln 3 p、Gat 1 p/Nil 1 p、Dal 80 p/Uga 43 p、Deh 1 p/GZF 3 p），其结合含GATA的 NCR敏感基因启动子中的序列。从几个聚合工作 实验室，包括我们自己的实验室，已经表明，当氮过量时， Gln 3 p和Gat 1 p被磷酸化并被排除在细胞核之外。当氮 由于限制，这些蛋白质不再磷酸化，变得定位于 细胞核，并介导NCR敏感的转录。我们建议继续 我们对GATA家族调节子的研究，进行实验， 阐明参与Gln 3 p、Gat 1 p和Gln 3 p调节的步骤和蛋白质， ure 2 p活性和细胞内定位。我们还将调查 Mks 1 p影响加塔调节子运作的机制。我们有 在我们的实验室建立了全基因组转录分析，并提出 识别：GATA因子调节子的新成员，成员 基因的调节，以及它们如何反过来调节GATA因子基因表达 和活动。发现了三个新的GATA因子Gat 2 p、Gat 3 p和Gat 4p in our pilot试点experiment实验.我们建议确定Gat 2 p的功能， 是与Gat 1 p在结构上最同源的GATA因子。我们还将 Gat 2 p本身是如何监管的。我们特别感兴趣的是 GATA-因子调节子组分与其它组分之间界面和整合 细胞内的调节系统。这个简单系统的复杂性 令人生畏，但将产生非常有用的信息和经验， 发展和解释更复杂的酵母和哺乳动物的研究 监管级联。