High-resolution dynamics of the transcriptional response to nutrition in Drosophila:: a key role for dFOXO

被引:140
作者
Gershman, Boris
Puig, Oscar
Hang, Lilian
Peitzsch, Robert M.
Tatar, Marc
Garofalo, Robert S.
机构
[1] Brown Univ, Div Biol & Med, Providence, RI 02912 USA
[2] Univ Helsinki, Inst Biotechnol, Helsinki, Finland
[3] Groton Labs, Pfizer Global Res & Dev, Groton, CT USA
关键词
metabolism; mitochondria; peroxisome proliferator-gamma coactivator-1; microarray; gene expression; insulin signaling; nutrient sensing; target of rapamycin pathway;
D O I
10.1152/physiolgenomics.00061.2006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:24 / 34
页数:11
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