REGULATION OF TISSUE-SPECIFIC GENE EXPRESSION

不同的细胞类型是由单个祖细胞在生长过程中形成的 发展 分化细胞的表型是由分化细胞的表型决定的。 选择的基因子集的表达。 事件的分子分析 调节单个基因细胞特异性表达的基因是一种 理解差异和发展的前提。 在许多 在某些情况下，组织特异性基因表达是由以下因素相互作用的结果： 增强子元件与启动子元件， 转录。 研究这一过程的一种方法是 这些相互作用被破坏的突变。 在果蝇中， 组织特异性突变是由插入一个转座因子引起的。 一个基因的元素。 在这些情况下，基因表达的改变是 由靶细胞中顺式连接的调节元件的调节引起 基因 调查 这种类型的诱变机制将提供信息， 理解和控制基因表达的基础。 这些研究的目的是分析几个 组织特异性增强子元件在指导转录中的作用 黄色基因 该基因是幼虫适当着色所必需的， 成体表皮和衍生结构。 的可见表型 该基因的突变导致了一种大的 改变成人色素沉着模式的等位基因数量 通过破坏正常的增强子功能来飞行。 这些实验将集中在理解的分子基础， 突变Y2。 在Y2果蝇中，插入700 bp的吉普赛元件， 黄色转录起始位点的上游引起组织特异性的 基因表达的改变。 这种诱变效应需要一种蛋白质， 毛翅（su（Hw））的抑制子，其具有已知的 转录因子 这项提案将研究如何su（Hw）蛋白 特异性地抑制身体和翅膀组织中的增强子功能。 将进行实验以检查su（Hw）蛋白是否可以 在黄色基因内的其他增强子元件，以及 和卵黄蛋白基因的组织特异性增强子元件。 这 将确定su（Hw）诱变的机制是否是灭活 在其结合位点远端的增强子元件。 其他特定模式 将检查转座元件诱导的low基因突变 以确定移动的元件是否共享共同的突变机制。 最后，等位基因间互补发生的基础 将研究Y2和黄色无效等位基因之间的关系。 这些实验 将阐明增强子元件激活 本文所述的研究将有助于 了解负责控制基因表达的机制 在有机体的发育过程中。

Diverse cell types are formed from a single progenitor cell during development. The phenotype of a differentiated cell results from the expression of a select subset of genes. Molecular analysis of events that regulate cell-specific expression of individual genes is a prerequisite for understanding differentiation and development. In many cases, tissue-specific gene expression results from the interaction of enhancer elements with promoter elements causing activation of transcription. One way to study this process is to characterize mutations in which these interactions are disrupted. In Drosophila, many tissue-specific mutations are caused by the insertion of a transposable element into a gene. In these cases, alteration of gene expression is caused by the modulation of cis-linked regulatory elements in the target gene. Investigation of mechanisms involved in this type of mutagenesis will provide information fundamental to understanding, control of gene expression. The goal of these studies is to analyze the role of several tissue-specific enhancer elements in directing transcription of the yellow gene. This gene is required for proper pigmentation of larval and adult cuticle and derivative structures. The visible phenotype of mutations in this gene has resulted in the identification of a large number of alleles which alter the pattern of pigmentation in the adult fly by disrupting normal enhancer function. These experiments will focus on understanding the molecular basis of the mutation y2. In y2 flies, insertion of a gypsy element 700 bp upstream of the yellow transcription start site causes a tissue-specific alteration of gene expression. This mutagenic effect requires a protein, suppressor of Hairy-wing (su(Hw)), which has characteristics of known transcription factors. This proposal will examine how the su(Hw) protein specifically inactivates enhancer function in body and wing tissues. Experiments will be carried out to examine if the su(Hw) protein can inactivate other enhancer elements within the yellow gene, as well as tissue- specific enhancer elements of the and yolk protein genes. This will determine if the mechanism of su(Hw) mutagenesis is the inactivation of enhancer elements distal to its binding site. Other pattern-specific transposable element-induced mutations of the low gene will be examined to determine if mobile elements share a common mutational mechanism. Lastly, the basis of the inter-allelic complementation which occurs between Y2 and yellow null alleles will be studied. These experiments will elucidate mechanisms by which enhancer elements activate transcription in trans. Studies described herein will contribute to the understanding of mechanisms responsible for controlling gene expression during the development of an organism.