GENETIC ANALYSIS OF YEAST GAL REGULATION

对面包酵母GAL基因进行了研究。cerevisae）提供了一个熟悉的， 真核基因调控机制的良好表征模型。 这些基因的表达通过两种方式调节： 半乳糖，并被葡萄糖抑制。 归纳的基础是 半乳糖是很好理解的，涉及阳性（GAL 4）和 负作用（GAL 80）蛋白。 葡萄糖的抑制作用 明白 它通过几种机制对GAL基因起作用： 1)它降低了源自半乳糖的诱导物的水平; 2）它 抑制GAL 4的表达，GAL 4编码转录 激活剂; 3）其通过URS序列直接抑制转录 在GAL基因启动子中。 葡萄糖抑制可以被看作是一种信号 转导机制，其中加入葡萄糖产生一个 最终影响基因调节蛋白功能的信号。 我们 长期目标是了解信号的性质， 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。 肿瘤发生是由于不受控制的 细胞生长，这在许多情况下是由基因表达改变引起的。 此外，由于葡萄糖是大多数细胞的关键营养素， 感知其可用性对于控制增长至关重要。 的 具体目标是： >阐明葡萄糖阻遏的机制。 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GAL 4转录是如何被抑制的， 葡萄糖 其次，我们打算解释抑制 通过GAL 1启动子中的URS元件直接转录。 第三，我们希望了解葡萄糖抑制的信号是如何产生的 通过识别和分析可能参与信号传导的基因， 一代 >鉴定葡萄糖诱导的基因表达所需的基因。 它 葡萄糖代谢机制的某些成分 基因表达的诱导和葡萄糖阻遏可能是共享的。 到 揭示这些成分，我们希望识别和分析所需的基因， 对这两种基因的调控。 这些基因可能与 信号生成 >了解更多关于GAL 4蛋白如何激活转录的信息。 几 具体的实验建议1）了解GAL 4蛋白如何识别 它的DNA结合位点，和2）识别与它相互作用的蛋白质， 激活转录。 >分析GAL 4启动子。 这一推动者是最弱的， 酵母 我们相信如果我们能理解为什么GAL 4启动子很弱， 我们将了解一些重要的转录机制， activation. 此外，我们希望确定转录 GAL 4的激活剂，因为我们相信它们可能是重要的 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.