Genome-wide Detection of Cell-specific Ecdysone Targets

细胞特异性蜕皮激素靶标的全基因组检测

• 批准号: 6937471
• 负责人: Melissa B Davis
• 金额: $ 4.4万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937471
• 关键词: Drosophilidae; arthropod genetics; binding sites; cell line; ecdysone; functional /structural genomics; gene expression; gene expression profiling; hormone regulation /control mechanism; postdoctoral investigator; receptor binding; steroid hormone receptor

DESCRIPTION (provided by applicant): This proposal discusses a project aimed at delineating the tissue-specific effects of the ecdysone steroid hormone. Generally, we aim to define the molecular mechanisms that regulate the dynamic responses observed in steroid hormone signaling. Steroids are naturally occurring molecules necessary for the development and homeostasis in animals and their derivatives are targets of many therapeutic treatments. We will use functional genomics to define a catalog of steroid hormone target genes on an entire genome scale. I will use whole genome tiling arrays to map genome wide DNA-protein interactions for the Ecdysone receptor using unique cell/tissue types. We will utilize computational techniques to examine both expression changes and EcR binding sites of target genes, ultimately revealing the tissue specific and/or EcR isoform specific gene targets. The tools refined during the completion of this endeavor will outline the backbone for a systematic large scale application to define similar catalogs of tissue-specific transcriptional regulators. These applications may be important for future studies where genomic analyses of gene expression are used to determine prognosis of hormone treatments and diagnosis of hormonal related disorders.

描述（由申请人提供）：该提案讨论了一个旨在描述蜕皮激素类固醇激素的组织特异性作用的项目。一般来说，我们的目标是定义调节类固醇激素信号传导中观察到的动态反应的分子机制。类固醇是动物发育和体内平衡所必需的天然分子，其衍生物是许多治疗的目标。我们将使用功能基因组学在整个基因组规模上定义类固醇激素靶基因的目录。我将使用全基因组平铺阵列，使用独特的细胞/组织类型来绘制蜕皮激素受体的全基因组 DNA-蛋白质相互作用图谱。我们将利用计算技术来检查靶基因的表达变化和 EcR 结合位点，最终揭示组织特异性和/或 EcR 亚型特异性基因靶标。在完成这项工作期间完善的工具将概述系统性大规模应用的支柱，以定义组织特异性转录调节因子的类似目录。这些应用对于未来的研究可能很重要，其中基因表达的基因组分析用于确定激素治疗的预后和激素相关疾病的诊断。