Promoter Regulation in Response to Environmental Stress

描述（由申请人提供）：生物体经常面临极端环境，包括温度，饥饿，辐射和有害化学物质。诱导基因已经进化来应对这些挑战。生物体还面临着日常的家务任务，如合成生物分子。 最近在芽殖酵母酿酒酵母的研究表明，真核生物通过两个不同的转录调控途径，分别由两个相关的转录机制，TFIID和佐贺的组成部分，平衡管家和应激反应的需要。了解一个基因是否主要由TFIID或佐贺调控，可以对其他转录调控因子的调控及其更广泛的细胞作用提供巨大的预测性见解。这种双重途径的许多方面仍有待阐明。TFIID/佐贺分类尚未在广泛的条件下进行，这些条件使基因组经历其全范围的表达，这对于所有基因的适当分类是必要的。虽然佐贺与应激诱导的基因表达有关，但尚不清楚其作用是否能保护细胞免受应激。被应激抑制的基因利用TFIID而不是佐贺，但人们对控制这一过程的启动子元件知之甚少。TATA盒也与应激反应有关。许多无TATA基因在其正常位置的上游有一个保守的TATA盒。它在基因调控中的潜在参与仍然未知。为了解决这些与生物体的应激反应密切相关的问题以及开发提高应激反应的治疗剂的潜力，提出了以下具体目标：1）对在广泛的环境应激下所有酵母基因的TFIID/SAGA依赖性进行分类。2)确定佐贺和/或TFIID是否提供应力保护。3)确定胁迫诱导基因阻遏的启动子决定簇。4)评估远上游TATA盒的功能。

DESCRIPTION (provided by applicant): Organisms are constantly faced with environmental extremes, involving temperature, starvation, radiation and harmful chemicals. Inducible genes have evolved to respond to these challenges. Organisms are also faced with day-to-day housekeeping tasks, such as synthesizing biomolecules. Recent studies in the budding yeast Saccharomyces cerevisiae suggest that eukaryotes balance housekeeping and stress-response needs through two distinct transcriptional regulatory pathways, represented by two related components of the transcription machinery, TFIID and SAGA, respectively. Knowing whether a gene is primarily regulated by TFIID or SAGA provides enormous predictive insight into its regulation by other transcriptional regulators, and its broader cellular role. Many aspects of this dual pathway remain to be elucidated. The TFIID/SAGA classification has not been conducted under a wide range of conditions that put the genome through its full range of expression, which is necessary for appropriate classification of all genes. While SAGA as been implicated in stress-induced gene expression, it is not known whether its action protects cells from stress. Genes repressed by stress utilize TFIID rather than SAGA, but little is known about what promoter elements control this process. The TATA box has also been implicated in the stress-response. Many TATA-less genes have a conserved TATA box far upstream of its normal location. It's potential involvement in gene regulation remains unknown. To address these problems which are germane to an organism's stress-response and the potential to develop therapeutic agents that heighten the stress response, the following specific aims are proposed: 1) Classify the TFIID/SAGA-dependence of all yeast genes under a wide range of environmental stresses. 2) Determine whether SAGA and/or TFIID provide stress protection. 3) Identify the promoter determinants of stressdirected gene repression. 4) Assess the function of far-upstream TATA boxes.