Genomic Targets of Drosophila Heat Shock Factor

果蝇热休克因子的基因组靶标

• 批准号: 138234-2013
• 负责人: Westwood, JonTimothy
• 金额: $ 2.62万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=593392
• 关键词: Genomic; Targets; Drosophila; Heat; Shock

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.

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)的被称为热休克(Hs)基因的转录来实现的。在正常和应激条件下，高度保守的HSPs及其同源蛋白具有帮助蛋白质正确折叠的重要功能，起到蛋白质“伴侣”的作用。热休克蛋白在许多疾病和病理生理状态中也具有直接和重要的功能。应激诱导的hs基因转录是由一种特殊的转录因子(S)介导的，该转录因子被称为热休克因子(S)(Hsf)，在应激时被转化为一种结合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起着重要作用。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在细胞中是否还有其他基因组靶点和/或作用？我们将通过实现以下具体目标来回答这一问题。特定目标1-确定HSF在应激过程中是否以及如何抑制果蝇中非hs基因的转录。特定目的2-确定HSF在果蝇正常发育过程中非hs基因转录中的作用。我们相信，这些概述的项目将识别由HSF调控的新基因，并对HSF的功能和调控提供见解。这项工作将提供对在所有生物体中发现的重要生物反应的全面功能基因组学观察。