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首页> 外文期刊>Genes & Genomics >Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcRnulln Drosophila melanogaster mutants
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Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcRnulln Drosophila melanogaster mutants

机译：使用蜕皮激素和EcRnulln果蝇黑变种突变体开始蜕皮激素甾体信号的基因组分析

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Steroid hormone gene regulation is often depicted as a linear transduction of the signal, from molecule release to the gene level, by activation of a receptor protein after being bound by its steroid ligand. Such an action would require that the hormone be present and bound to the receptor in order to have target gene response. Here, we present data that presents a novel perspective of hormone gene regulation, where the hormone molecule and its receptor have exclusive target gene regulation function, in addition to the traditional direct target genes. Our study is the first genome-wide analysis of conditional mutants simultaneously modeling the steroid and steroid receptor gene expression regulation. We have integrated classical genetic mutant experiments with functional genomics techniques in the Drosophila melanogaster model organism, where we interrogate the 20-hydroxyecdysone signaling response at the onset of metamorphosis. Our novel catalog of ecdysone target genes illustrates the separable transcriptional responses among the hormone, the pre-hormone receptor and the post-hormone receptor. We successfully detected traditional ecdysone target genes as common targets and also identified novel sets of target genes which where exclusive to each mutant condition. Around 12% of the genome responds to the ecdysone hormone signal at the onset of metamorphosis and over half of these are independent of the receptor. In addition, a significant portion of receptor regulated genes are differentially regulated by the receptor, depending on its ligand state. Gene ontology enrichment analyses confirm known ecdysone regulated biological functions and also validate implicated pathways that have been indirectly associated with ecdysone signaling.
机译：类固醇激素基因调控通常被描述为信号的线性传导，从分子释放到基因水平，是通过受体蛋白与类固醇配体结合后的激活来实现的。这种作用将要求激素存在并与受体结合，以产生靶基因应答。在这里，我们提供的数据提出了激素基因调控的新观点，其中激素分子及其受体除传统的直接靶基因外，还具有排他的靶基因调控功能。我们的研究是同时对类固醇和类固醇受体基因表达调控进行建模的条件突变体的首次全基因组分析。我们已经在果蝇模型生物中整合了具有功能基因组学技术的经典遗传突变实验，并在变态发生时询问了20-羟基蜕皮激素的信号响应。我们新的蜕皮激素靶基因目录阐明了激素，激素前受体和激素后受体之间的可分离转录反应。我们成功地检测到传统的蜕皮激素目标基因为常见目标，并且还鉴定了新的目标基因组，这些基因在每种突变条件下都是唯一的。大约12％的基因组在蜕变开始时对蜕皮激素信号产生响应，其中一半以上与受体无关。另外，取决于受体的配体状态，受体调节基因的很大一部分受受体差异调节。基因本体富集分析证实了蜕皮激素调节的生物学功能，并且还验证了与蜕皮激素信号传导间接相关的牵连途径。

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