Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element.
Nutritional control of gene expression in Drosophila larvae via TOR, Myc and a novel cis-regulatory element.
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DOI：
10.1186/1471-2121-11-7
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发表时间：
2010-01-20
期刊：
影响因子：
--
通讯作者：
Grewal SS
中科院分区：
文献类型：
--
作者：
Li L;Edgar BA;Grewal SS
营养可利用性是真核细胞生长的关键决定因素。在单细胞生物中，许多信号和转录网络将营养可利用性与生长所需的代谢基因的表达联系起来。然而，对后生动物的相应机制知之甚少。我们使用基因表达谱来探讨发育中的果蝇幼虫的这一问题。我们发现，对膳食氨基酸（AA's）的饥饿导致许多代谢基因转录水平的动态变化。保守的胰岛素/PI3K和TOR信号通路介导果蝇和其他动物的营养依赖性生长。我们发现许多AA饥饿应答转录本在TOR突变体中也发生了改变。相比之下，尽管PI3K过表达诱导了许多代谢基因表达的强烈变化，但这些变化与AA饥饿表达谱的重叠程度有限。然而，我们确实发现了转录因子Myc和AA饥饿反应基因调控的基因之间存在强烈的重叠，特别是那些参与核糖体生物发生、蛋白质合成和线粒体功能的基因。普遍认为Myc DNA结合位点富含这些AA饥饿基因的启动子，我们发现Myc过表达可以绕过膳食AA诱导这些基因的表达。我们还在AA饥饿应答基因的启动子中发现了另一个序列基序（motif 1）。结果表明，Motif 1在介导幼虫对AA的转录反应中是必要和充分的。我们的数据表明，在果蝇幼虫中，氨基酸的许多转录作用是通过TOR通路的信号传导介导的。我们还发现这些转录效应至少通过两种机制介导：通过转录因子Myc和Motif 1顺式调控元件。这些研究开始阐明控制果蝇代谢基因转录的营养反应信号网络。
Nutrient availability is a key determinant of eukaryotic cell growth. In unicellular organisms many signaling and transcriptional networks link nutrient availability to the expression of metabolic genes required for growth. However, less is known about the corresponding mechanisms that operate in metazoans. We used gene expression profiling to explore this issue in developing Drosophila larvae. We found that starvation for dietary amino acids (AA's) leads to dynamic changes in transcript levels of many metabolic genes. The conserved insulin/PI3K and TOR signaling pathways mediate nutrition-dependent growth in Drosophila and other animals. We found that many AA starvation-responsive transcripts were also altered in TOR mutants. In contrast, although PI3K overexpression induced robust changes in the expression of many metabolic genes, these changes showed limited overlap with the AA starvation expression profile. We did however identify a strong overlap between genes regulated by the transcription factor, Myc, and AA starvation-responsive genes, particularly those involved in ribosome biogenesis, protein synthesis and mitochondrial function. The consensus Myc DNA binding site is enriched in promoters of these AA starvation genes, and we found that Myc overexpression could bypass dietary AA to induce expression of these genes. We also identified another sequence motif (Motif 1) enriched in the promoters of AA starvation-responsive genes. We showed that Motif 1 was both necessary and sufficient to mediate transcriptional responses to dietary AA in larvae. Our data suggest that many of the transcriptional effects of amino acids are mediated via signaling through the TOR pathway in Drosophila larvae. We also find that these transcriptional effects are mediated through at least two mechanisms: via the transcription factor Myc, and via the Motif 1 cis-regulatory element. These studies begin to elucidate a nutrient-responsive signaling network that controls metabolic gene transcription in Drosophila.
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