REGULATION OF TISSUE-SPECIFIC GENE EXPRESSION

不同类型的细胞是由单个祖细胞在 发展。分化细胞的表型是由 特定基因子集的表达。事件的分子分析 调节单个基因的细胞特异性表达是一种 了解分化和发展的前提条件。在许多 例如，组织特异性基因的表达是由 具有启动子元件的增强子元件可导致激活 抄写。研究这一过程的一种方法是将 这些相互作用被破坏的突变。在果蝇中，许多 组织特异性突变是由插入可转座子引起的 元素注入到基因中。在这些情况下，基因表达的改变是 由靶标中顺式连接的调控元件的调制引起 吉恩。调查 这种类型的突变所涉及的机制将提供信息 了解和控制基因表达的基础。 这些研究的目标是分析几个 组织特异性增强子元件在指导转录中的作用 黄色基因。这种基因是幼虫正常着色所必需的，而且 成体角质层及其衍生结构。可见的表型 这种基因的突变导致了一种大型的 改变成人色素沉着模式的等位基因数目 通过扰乱正常的增强剂功能来飞行。 这些实验将集中于了解分子基础 突变基因y2。在y2果蝇中，插入一个700bp的吉普赛元件 黄色转录起始点的上游引起组织特异性 基因表达的改变。这种突变效应需要一种蛋白质， 毛翅抑制因子(SU(HW))，具有已知的特征 转录因子。这项提案将研究SU(HW)蛋白是如何 特别是使身体和翅膀组织中的增强器功能失活。 将进行实验以检验su(Hw)蛋白是否可以 使黄色基因内的其他增强子元件失活，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)突变的机制是否是失活 位于其结合部位远端的增强子元件。其他特定于模式的 将检测转座元件诱导的低基因突变。 以确定移动元素是否具有共同的突变机制。 最后，发生等位基因间互补的基础 Y2和黄色零等位基因之间的关系将被研究。这些实验 将阐明增强子元件激活的机制 转译的转录。这里描述的研究将有助于 对基因表达调控机制的理解 在生物体的发育过程中。

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.