Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcRnullDrosophila melanogaster mutants.
Genomic analysis of the ecdysone steroid signal at metamorphosis onset using ecdysoneless and EcRnullDrosophila melanogaster mutants.
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DOI：
10.1007/s13258-013-0061-0
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发表时间：
2013-02
期刊：
影响因子：
2.1
通讯作者：
中科院分区：
文献类型：
--
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类固醇激素基因调控通常被描述为信号的线性转导，从分子释放到基因水平，通过受体蛋白被类固醇配体结合后的激活。这种作用需要激素存在并与受体结合，以产生靶基因反应。在这里，我们提供的数据提出了激素基因调控的新视角，激素分子及其受体除了传统的直接靶基因外，还具有独特的靶基因调控功能。我们的研究是第一个同时模拟类固醇和类固醇受体基因表达调控的条件突变体的全基因组分析。我们将经典的基因突变实验与功能基因组学技术结合起来，在果蝇模型生物中，我们在变态开始时询问20-羟基蜕皮激素信号反应。我们新的蜕皮激素靶基因目录说明了激素、激素前受体和激素后受体之间可分离的转录反应。我们成功地检测到传统的蜕皮激素靶基因作为共同的靶点，也发现了新的靶基因组，这些靶基因组在每种突变条件下都是专有的。大约12%的基因组在变态开始时对蜕皮激素信号作出反应，其中一半以上与受体无关。此外，很大一部分受体调节基因受受体的差异调节，取决于其配体状态。基因本体富集分析证实了已知的蜕皮激素调节的生物学功能，也证实了与蜕皮激素信号间接相关的相关途径。本文的在线版本（doi:10.1007/s13258-013-0061-0）包含补充资料，仅供授权用户使用。
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. The online version of this article (doi:10.1007/s13258-013-0061-0) contains supplementary material, which is available to authorized users.
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影响因子：
4.6
作者：
Cherbas, L;Hu, X;Cherbas, P
通讯作者：
Cherbas, P
影响因子：
4.6
作者：
Brown, HLD;Cherbas, L;Truman, JW
通讯作者：
Truman, JW
影响因子：
1.6
作者：
ASHBURNER, M
通讯作者：
ASHBURNER, M
影响因子：
2.7
作者：
ASHBURNER, M
通讯作者：
ASHBURNER, M
影响因子：
4.8
作者：
BLACKMORE, PF
通讯作者：
BLACKMORE, PF