MECHANISM OF REGULATION OF HEAT SHOCK GENE EXPRESSION

胚胎发育、细胞分化或适应等过程 细胞进入新环境的过程中， 各种基因的表达。 我们对这些过程的理解是 因此关键取决于我们对分子机制的了解 基因调控。 在这项研究中，果蝇热休克蛋白 基因被用作研究基因调控方面的模型系统， 以上几个过程。 热休克蛋白基因似乎 在每一个活的有机体中， 其中一些是高度保守的。 这些基因的表达 在升高的温度下处于高水平，并且在 正常的，生理温度的有机体，和他们的一个作用， 产品似乎是保护细胞免受压力引起的损害。 的 基因也在正常发育的不同阶段表达。 以来 至少一种基因被不同的转化基因激活， 因为人类基因在达到的温度下最活跃， 在高烧期间或在癌症的热疗期间， 关于这些基因及其调控的信息不仅是一般的 但它可能在医学上具有实际意义。 其中E.大肠杆菌β-半乳糖苷酶编码区已被 置于连接的热休克蛋白基因启动子的控制下， 序列已经构建。 这些杂交基因可以被引入到 果蝇细胞，当它们被激活时， β-半乳糖苷酶。 热诱导表达的两个和 这些杂合基因之一的发育调控以及 含有启动子片段的基因已经在体外被改变， 将在合适的果蝇组织中检查序列操作 培养系统和发育中的生物体（引入杂交基因 通过P-元件介导的转化进入种系）。 这项工作将 定义负责发育的信号序列， 热激蛋白基因的热诱导活化。 实验以确定涉及热的新因素， 热休克基因表达的发育调控。

Processes such as embryonic development, cell differentiation or adaptation of cells to new environments all involve changes in the levels of expression of various genes. Our understanding of these processes is therefore critically dependent on our knowledge of the molecular mechanisms of gene regulation. In the research described in this proposal, Drosophila heat shock protein genes are used as model system for studying aspects of gene regulation in several of the above processes. Heat shock protein genes appear to occur in every living organism, and the structures of the protein products of some of them are highly conserved. The genes are expressed at exceedingly high levels at elevated temperature and typically at very low levels at the normal, physiological temperature of an organism, and one role of their products appears to be to protect cells against stress-induced damage. The genes are also expressed at different stages of normal development. Since at least one of the genes is activated by different transforming genes and since the human genes are maximally active at temperatures that are reached during periods of high fever or during hyperthermic treatments of cancers, information about these genes and their regulation are not only of general interest but may even become of practical importance in medicine. Hybrid genes in which the E. coli Beta-galactosidase coding region has been placed under the control of linked heat shock protein gene promoter sequences have been constructed. These hybrid genes can be introduced into Drosophila cells where, when activated, they direct the synthesis of Beta-galactosidase. The heat-induced expression of two and the developmental regulation of one of these hybrid genes and of derivatives of the genes containing promoter segments that have been altered by in vitro sequence manipulation will be examined in a suitable Drosophila tissue culture system and in the developing organism (hybrid genes are introduced into the germline by P-element-mediated transformation). This work will define the signal sequences responsible for the developmental and heat-induced activation of heat shock protein genes. Experiments to identify novel factors involved in the heat and developmental control of heat shock gene expression are proposed.