GENETIC ANALYSIS OF YEAST GAL REGULATION

面包酵母(S.cerevisae)的Gal基因提供了一种熟悉的和 描述真核生物基因调控机制的良好模型。 这种基因的表达受两种方式的调节：它是由 半乳糖，并被葡萄糖抑制。归纳的基础是 半乳糖是众所周知的，包括正(GAL4)和 负作用(GAL80)蛋白。葡萄糖抑制就不那么好了 明白了。它通过几种机制作用于半乳糖基因： 1)它降低了来自半乳糖的诱导剂的水平；2)它 抑制GAL4的表达，GAL4编码转录 激活剂；3)通过URS序列直接抑制转录 在GAL基因启动子中。葡萄糖抑制可以被视为一种信号 转导机制，由此添加葡萄糖产生一种 最终影响基因调控蛋白功能的信号。我们的 长期目标是理解信号的性质，它是如何 从葡萄糖中产生，以及它最终如何影响基因表达。 我们相信，这将提供与增长相关的基本知识 控制更复杂的生物体。肿瘤的发生是由于失控 细胞生长，这在许多情况下是由基因表达变化引起的。 此外，由于葡萄糖是大多数细胞的关键营养物质，因此 感觉到它的可用性对于控制增长至关重要。这个 具体目标是： &gt；以阐明葡萄糖抑制的机制。这一目标将说明 对于我们的大部分努力，可以分为三个项目。 首先，我们希望了解GAL4转录是如何被抑制的 葡萄糖。第二，我们打算解释抑制的机制 直接通过GAL1启动子中的URS元件转录。 第三，我们希望了解葡萄糖抑制信号是如何产生的 通过识别和分析可能与信号有关的基因 一代。 &gt；以确定葡萄糖诱导基因表达所需的基因。它 似乎有可能葡萄糖机制的一些成分 基因表达的诱导和葡萄糖抑制可能是共同的。至 揭示这样的成分，我们希望能够识别和分析所需的基因 用于调节这两种类型的基因。这些基因可能参与了 信号产生。 &gt；了解有关GAL4蛋白如何激活转录的更多信息。几个 具体的实验是为了1)了解GAL4蛋白如何识别 它的DNA结合部位，以及2)识别它与之相互作用的蛋白质 启动转录。 &gt；分析GAL4启动子。这个推动者是世界上最弱的 酵母菌。我们相信，如果我们能理解为什么GAL4启动子很弱， 我们将学到一些关于转录机制的重要知识。 激活。此外，我们希望确定转录的 GAL4的激活剂，因为我们认为它们很可能是重要的 酵母中的转录因子。

The GAL genes of bakers' yeast (S. cerevisae) provide a familiar and well-characterized model for mechanisms of eukaryotic gene regulation. Expression of thise genes is regulated in two ways: it is induced by galactose, and repressed by glucose. The basis for induction by galactose is well-understood, involving both positively (GAL4) and negatively-acting (GAL80) proteins. Glucose repression is less well understood. It iperates upon the GAL genes through several mehanisms: 1) it reduces the level of the inducer derived from galactose; 2) it represses expression of GAL4, which encodes the transcriptional activator; 3) it directly inhibits transcription through URS sequences in the GAL gene promoters. Glucose repression can be viewed as a signal transduction mechanism, whereby the addition of glucose generates a signal that ultimately affects function of gene regulatory proteins. Our long-term goals are to understand the nature of the signal, how it is generated from glucose, and how it eventually effects gene expression. We believe this will provide fundamental knowledge relevant to growth control of more complex organisms. Tumorigenesis is due to uncontrolled cell growth, which in many cases is caused by altered gene expression. In addition, since glucose is a key nutrient for most cells, the ability to sense its availability is critical for controlling growth. The specific aims are: >To elucidate mechanisms of glucose repression. This aim will account for the majority of our efforts, and can be divided into three projects. First, we wish to understand how GAL4 transcription is repressed by glucose. Second, we intend to explain the mechanisms that inhibit transcription directly through the URS elements in the GAL1 promoter. Third, we hope to learn how the signal for glucose repression is produced by identifying and analyzing genes that might be involved in signal generation. >To identify genes required for glucose-induced gene expression. It seems possible that some of the components of mechanisms of glucose induction and glucose repression of gene expression might be shared. To reveal such components, we hope to identify and analyze genes required for regulation of both types of genes. Such genes could be involved in signal generation. >To learn more about how GAL4 protein activates transcription. A few specific experiments are proposed to 1) learn how GAL4 protein recognizes its DNA binding site, and 2) to identify proteins it interacts with to activate transcription. >To analyze the GAL4 promoter. This promoter is among the weakest in yeasts. We believe if we can understand why the GAL4 promoter is weak, we will learn something important abour mechanisms of transcriptional activation. In addition, we wish to identify the transcriptional activators of GAL4, because we believe thay are likely to be important transcription factors in yeasts.