Genomic Targets of Drosophila Heat Shock Factor

所有生物体对高温和其他形式的压力的反应都是通过诱导编码热休克蛋白（hsps）的热休克（hs）基因的转录来实现的。 在正常和应激条件下，高度保守的热休克蛋白及其同源蛋白具有帮助蛋白质正确折叠的重要功能，充当蛋白质“伴侣”。热休克蛋白还被认为在许多疾病和病理生理状态中具有直接和重要的功能。应激诱导的hs基因转录由称为热休克因子（HSF）的特异性转录因子介导，其在应激时转化为结合hs基因启动子的活性形式。HSF也被证明在发育和肿瘤发生中具有重要作用。我们希望解决的一个主要问题是-除了在应激过程中诱导众所周知的hs基因外，HSF在细胞中是否有任何其他基因组靶点和/或作用？ 我们将通过实现以下具体目标来回答这个问题。具体目标1-确定是否以及如何HSF抑制果蝇在应激过程中的非hs基因的转录。 具体目标2-确定在正常果蝇发育过程中HSF在非hs基因转录中的作用。我们相信，概述的项目将确定由HSF调控的新基因，并深入了解HSF的功能和调控。这项工作将提供一个全面的功能基因组研究在所有生物体中发现的重要生物反应。

All organisms respond to elevated temperatures and other forms of stress by inducing the transcription of genes known as the heat shock (hs) genes that encode heat shock proteins (hsps). During normal and stressed conditions, the highly conserved hsps and their cognate proteins have essential functions in helping proteins fold properly, acting as protein "chaperones". Hsps are also known to have direct and important functions in a number of diseases and pathophysiological states. Stress induced transcription of the hs genes is mediated by a specific transcription factor(s) known as heat shock factor(s) (HSF) which upon stress, is converted to an active form that binds the promoters of hs genes. HSF has also been shown to have important roles in development and tumorigenesis. A major question we hope to address is- Does HSF have any other genomic targets and/or roles in the cell besides the induction of the well known hs genes during stress? We will answer this by accomplishing the following specific aims. Specific Aim 1- To determine if and how HSF represses the transcription of non-hs genes in Drosophila during stress. Specific Aim 2- To determine the role of HSF in the transcription of non-hs genes during normal Drosophila development. We believe the projects outlined will identify new genes regulated by HSF and give insights into HSF function and regulation. This work will provide a comprehensive functional genomic look at a vital biological response that is found in all organisms.