High-resolution dynamics of the transcriptional response to nutrition in Drosophila:: a key role for dFOXO
High-resolution dynamics of the transcriptional response to nutrition in Drosophila:: a key role for dFOXO
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DOI：
10.1152/physiolgenomics.00061.2006
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发表时间：
2007-03-14
影响因子：
4.6
通讯作者：
Garofalo, Robert S.
中科院分区：
文献类型：
--
作者：
Gershman, Boris;Puig, Oscar;Garofalo, Robert S.
一个高分辨率的时间序列的转录丰度来描述全球表达动态响应营养果蝇。非参数变化点统计显示，在7小时内喂养酵母，转录水平发生显着变化，约3,500个基因或20%的果蝇基因组。小至15%的差异都非常显着，80%的变化< 1.5倍。值得注意的是，转录变化反映了营养敏感胰岛素和雷帕霉素途径靶点的快速下调，燃料代谢从脂质向葡萄糖氧化的转变，以及嘌呤合成、TCA生物合成功能和线粒体生物合成的增加。为了研究营养如何协调这些转录变化，将喂食诱导的表达变化与果蝇S2细胞中胰岛素调节转录因子dFOXO诱导的表达变化进行了比较。值得注意的是，28%（995）的营养响应基因受激活的dFOXO调控，包括线粒体生物发生基因和哺乳动物过氧化物酶体增殖物-γ共激活因子-1（PGC-1）的新型同系物，PGC-1是一种转录共激活因子，参与控制哺乳动物线粒体基因表达。这些数据暗示dFOXO作为胰岛素下游营养素转录反应的主要协调者，并表明线粒体生物合成通过dFOXO介导的PGC-1同源物抑制与胰岛素信号传导相关。
A high-resolution time series of transcript abundance was generated to describe global expression dynamics in response to nutrition in Drosophila. Nonparametric change-point statistics revealed that within 7 h of feeding upon yeast, transcript levels changed significantly for similar to 3,500 genes or 20% of the Drosophila genome. Differences as small as 15% were highly significant, and 80% of the changes were < 1.5-fold. Notably, transcript changes reflected rapid downregulation of the nutrient-sensing insulin and target of rapamycin pathways, shifting of fuel metabolism from lipid to glucose oxidation, and increased purine synthesis, TCA-biosynthetic functions and mitochondria biogenesis. To investigate how nutrition coordinates these transcriptional changes, feeding-induced expression changes were compared with those induced by the insulin-regulated transcription factor dFOXO in Drosophila S2 cells. Remarkably, 28% (995) of the nutrient-responsive genes were regulated by activated dFOXO, including genes of mitochondrial biogenesis and a novel homolog of mammalian peroxisome proliferator-gamma coactivator-1 (PGC-1), a transcriptional coactivator implicated in controlling mitochondrial gene expression in mammals. These data implicate dFOXO as a major coordinator of the transcriptional response to nutrients downstream of insulin and suggest that mitochondria biogenesis is linked to insulin signaling via dFOXO-mediated repression of a PGC-1 homolog.