Alic, N and Andrews, TD and Giannakou, ME and Papatheodorou, I and Slack, C and Hoddinott, MP and Cocheme, HM and Schuster, EF and Thornton, JM and Partridge, L (2011) Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. MOL SYST BIOL , 7 , Article 502. 10.1038/msb.2011.36.
FoxO transcription factors, inhibited by insulin/insulin-like growth factor signalling (IIS), are crucial players in numerous organismal processes including lifespan. Using genomic tools, we uncover over 700 direct dFOXO targets in adult female Drosophila. dFOXO is directly required for transcription of several IIS components and interacting pathways, such as TOR, in the wild-type fly. The genomic locations occupied by dFOXO in adults are different from those observed in larvae or cultured cells. These locations remain unchanged upon activation by stresses or reduced IIS, but the binding is increased and additional targets activated upon genetic reduction in IIS. We identify the part of the IIS transcriptional response directly controlled by dFOXO and the indirect effects and show that parts of the transcriptional response to IIS reduction do not require dfoxo. Promoter analyses revealed GATA and other forkhead factors as candidate mediators of the indirect and dfoxoindependent effects. We demonstrate genome-wide evolutionary conservation of dFOXO targets between the fly and the worm Caenorhabditis elegans, enriched for a second tier of regulators including the dHR96/daf-12 nuclear hormone receptor. Molecular Systems Biology 7: 502; published online 21 June 2011; doi:10.1038/msb.2011.36
|Title:||Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling|
|Open access status:||An open access publication|
|Publisher version:||http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3159968/?tool=pubmed|
|Keywords:||dFOXO, Drosophila, insulin/insulin-like growth factor signalling, transcription, LIFE-SPAN EXTENSION, PROBE LEVEL DATA, CAENORHABDITIS-ELEGANS, C-ELEGANS, DIETARY RESTRICTION, OXIDATIVE-STRESS, CELL HOMEOSTASIS, DROSOPHILA-FOXO, HUMAN LONGEVITY, FAT-BODY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Genetics, Evolution and Environment|
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