Genome-wide Detection of Cell-specific Ecdysone Targets

描述（由申请人提供）：本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，我们的目标是确定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性治疗的靶点。我们将使用功能基因组学来定义一个类固醇激素靶基因在整个基因组规模的目录。我将使用全基因组平铺阵列，使用独特的细胞/组织类型绘制蜕皮激素受体的全基因组DNA-蛋白质相互作用。我们将利用计算技术来研究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亚型特异性基因靶点。在完成这一奋进过程中完善的工具将勾勒出一个系统的大规模应用的骨干，以定义组织特异性转录调节因子的类似目录。这些应用程序可能是重要的未来的研究中，基因表达的基因组分析用于确定激素治疗和激素相关疾病的诊断预后。

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.