Genome-wide Detection of Cell-specific Ecdysone Targets

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效应的项目。总的来说，我们的目标是定义调节类固醇激素信号中观察到的动态反应的分子机制。类固醇是动物体内发育和动态平衡所必需的天然分子，其衍生物是许多治疗方法的靶点。我们将使用功能基因组学在整个基因组范围内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，通过独特的细胞/组织类型绘制蜕皮激素受体的全基因组DNA-蛋白质相互作用图。我们将利用计算技术来检测目标基因的表达变化和ECR结合部位，最终揭示组织特异性和/或ECR异构体特异性的基因靶点。在完成这项工作的过程中改进的工具将勾勒出系统的大规模应用的主干，以定义类似的组织特异性转录调控因子目录。这些应用可能对未来的研究很重要，在这些研究中，基因表达的基因组分析被用来确定激素治疗的预后和激素相关疾病的诊断。

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.