DAX1 regulatory networks unveil conserved and potentially new functions
DAX1 regulatory networks unveil conserved and potentially new functions
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DOI：
10.1016/j.gene.2013.07.052
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发表时间：
2013-11-01
期刊：
影响因子：
3.5
通讯作者：
Canario, Adelino V. M.
中科院分区：
文献类型：
--
作者：
Martins, Rute S. T.;Power, Deborah M.;Canario, Adelino V. M.
DAX1 是一种孤儿核受体，在哺乳动物性别决定、类固醇生成调节、胚胎发育和神经分化中发挥作用。从哺乳动物到鱼类，DAX1 基因表达的保守模式表明其功能是保守的。在本研究中，分离了欧洲鲈鱼（Dicentrarchus labrax）的DAX1启动子，并将其与其他鱼类和哺乳动物DAX1启动子相比的保守特征进行比较，以便衍生出共同的调节因子和功能基因网络。鱼类和哺乳动物 DAX1 启动子共享一组共同的转录因子框架，这些框架也存在于另外 127 个基因的启动子区域中。通路分析将这些聚类到与鱼类和哺乳动物 DAX1 相关的候选基因网络中。确定的网络与 DAX1 在胚胎发生、转录调节、内分泌发育和类固醇产生中的描述功能一致。还确定了新的候选基因网络伙伴，这表明 DAX1 参与离子稳态和运输、脂质运输和骨骼发育。实验证据支持 DAX1 在鱼类类固醇信号传导和渗透调节中的作用。这些结果强调了计算机比较方法分析基因调控以生成假设的有用性。保守的启动子结构也可用于预测潜在的新基因功能。报告的方法可应用于模型和非模型物种的基因。 (C) 2013 Elsevier B.V. 保留所有权利。
DAX1 is an orphan nuclear receptor with actions in mammalian sex determination, regulation of steroidogenesis, embryonic development and neural differentiation. Conserved patterns of DAX1 gene expression from mammals to fish have been taken to suggest conserved function. In the present study, the European sea bass, Dicentrarchus labrax, DAX1 promoter was isolated and its conserved features compared to other fish and mammalian DAX1 promoters in order to derive common regulators and functional gene networks. Fish and mammalian DAX1 promoters share common sets of transcription factor frameworks which were also present in the promoter region of another 127 genes. Pathway analysis clustered these into candidate gene networks associated with the fish and mammalian DAX1. The networks identified are concordant with described functions for DAX1 in embryogenesis, regulation of transcription, endocrine development and steroid production. Novel candidate gene network partners were also identified, which implicate DAX1 in ion homeostasis and transport, lipid transport and skeletal development. Experimental evidence is provided supporting roles for DAX1 in steroid signalling and osmoregulation in fish. These results highlight the usefulness of the in silico comparative approach to analyse gene regulation for hypothesis generation. Conserved promoter architecture can be used also to predict potentially new gene functions. The approach reported can be applied to genes from model and non-model species. (C) 2013 Elsevier B.V. All rights reserved.