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

Our analysis describes the transcriptional dynamics of metabolic and physiological networks across the initial 12 h of this physiological response

Boris Gershman; Oscar Puig; Lilian Hang; Robert M. Peitzsch; Marc Tatar; Robert S. Garofalo

2006

Scholarcy highlights

  • A high-resolution time series of transcript abundance was generated to describe global expression dynamics in response to nutrition in Drosophila
  • Depending on the interactions with endogenous substrates, which are unknown, the transcription changes in the FK506 proteins along with those in Rheb and S6 kinase may desensitize the dTOR pathway to nutrient stimuli upon refeeding, much as we propose for insulin signaling within cells
  • Beside a parallel based on sequence, orthologous targets of PGC-1 were elevated in refed flies and were reduced by dFOXO-A3 in S2 cells, including mitochondrial transcription factor A
  • This suggests that upon feeding, release of insulin ligands induces an acute yet widespread response via modulation of dFOXO activity. It remains to be determined whether dFOXO affects the >900 candidate target genes directly or indirectly and to understand the relative contribution of induction vs. message stability and degradation in determining how transcript abundance changes with nutrient uptake
  • To assess the potential for dFOXO to act as the direct transcription factor of these candidate genes we searched for sequence patterns enriched in their promoter regions
  • Of 60 nuclear encoded mitochondrial ribosomal genes on the array, expression of 54 was increased an average of 44% at 5–7 h after refeeding
  • Two clusters of genes can be defined in Table S4: those whose expression increases in S2 cells with activated dFOXO and decreases upon yeast refeeding and those that decrease in dFOXO-A3 cells and increase with refeeding
  • Patterns with significant enrichment were screened with the JASPAR database to identify recognized transcription factor binding sites

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