High-resolution dynamics of the transcriptional response to nutrition in Drosophila: a key role for dFOXO.
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 approximately 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.
Gershman
Boris
B
Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA.
Puig
Oscar
O
Hang
Lilian
L
Peitzsch
Robert M
RM
Tatar
Marc
M
Garofalo
Robert S
RS
D000824:Animal Nutritional Physiological Phenomena / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism* / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000378:metabolism / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism* / Q000494:pharmacology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015003:Yeasts
D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1