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Physiol. Genomics 29: 24-34, 2007. First published November 7, 2006; doi:10.1152/physiolgenomics.00061.2006
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High-resolution dynamics of the transcriptional response to nutrition in Drosophila: a key role for dFOXO

¹ Division of Biology and Medicine, Brown University, Providence, Rhode Island
² Institute of Biotechnology, University of Helsinki, Helsinki, Finland
³ Pfizer Global Research and Development, Groton Labs, Groton, Connecticut

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 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- 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.

metabolism; mitochondria; peroxisome proliferator- coactivator-1; microarray; gene expression; insulin signaling; nutrient sensing; target of rapamycin pathway

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