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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene expression
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Heterodimer of two bHLH-PAS proteins mediates juvenile hormone-induced gene expression

机译：两种bHLH-PAS蛋白的异二聚体介导少年激素诱导的基因表达

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摘要

Juvenile hormone (JH) plays crucial roles in many aspects of insect life. The Methoprene-tolerant (Met) gene product, a member of the bHLH-PAS family of transcriptional regulators, has been demonstrated to be a key component of the JH signaling pathway. However, the molecular function of Met in JH-induced signal transduction and gene regulation remains to be fully elucidated. Here we show that a transcriptional coactivator of the ecdysteroid receptor complex, FISC, acts as a functional partner of Met in mediating JH-induced gene expression. Met and FISC appear to use their PAS domains to form a dimer only in the presence of JH or JH analogs. In newly emerged adult female mosquitoes, expression of some JH responsive genes is considerably dampened when Met or FISC is depleted by RNAi. Met and FISC are found to be associated with the promoter of the early trypsin gene (AaET) when transcription of this gene is activated by JH. A juvenile hormone response element (JHRE) has been identified in the AaET upstream regulatory region and is bound in vitro by the Met-FISC complex present in the nuclear protein extracts of previtellogenic adult female mosquitoes. In addition, the Drosophila homologs of Met and FISC can also use this mosquito JHRE to activate gene transcription in response to JH in a cell transfection assay. Together, the evidence indicates that Met and FISC form a functional complex on the JHRE in the presence of JH and directly activate transcription of JH target genes.
机译：幼体激素（JH）在昆虫生活的许多方面都起着至关重要的作用。已证明bHLH-PAS转录调节子家族的成员甲氧戊二烯耐受（Met）基因产物是JH信号通路的关键组成部分。但是，Met在JH诱导的信号转导和基因调控中的分子功能仍有待充分阐明。在这里，我们显示蜕皮甾类受体复合物FISC的转录共激活因子在介导JH诱导的基因表达中作为Met的功能伙伴。 Met和FISC似乎仅在JH或JH类似物存在时才使用其PAS域形成二聚体。在新出现的成年雌性蚊子中，当Met或FISC被RNAi耗尽时，某些JH响应基因的表达会大大减弱。当JH激活该基因的转录时，发现Met和FISC与早期胰蛋白酶基因（AaET）的启动子相关。在AaET上游调节区中已经确定了一个少年激素反应元件（JHRE），并在体外与成胎前成年雌性蚊子核蛋白提取物中存在的Met-FISC复合物结合。此外，Met和FISC的果蝇同源物还可以在细胞转染测定中使用这种蚊子JHRE激活响应JH的基因转录。总之，证据表明在JH存在下，Met和FISC在JHRE上形成功能复合物，并直接激活JH目标基因的转录。

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