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Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling

Alic, N; Andrews, TD; Giannakou, ME; Papatheodorou, I; Slack, C; Hoddinott, MP; Cocheme, HM; ... Partridge, L; + view all (2011) Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Molecular Systems Biology , 7 , Article 502. 10.1038/msb.2011.36. Green open access

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Abstract

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

Type: Article
Title: Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/msb.2011.36
Publisher version: http://dx.doi.org/10.1038/msb.2011.36
Language: English
Additional information: This work is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, CC BY-NC-SA (http://creativecommons.org/licenses/by-nc-sa/3.0/). You may share (copy, distribute and transmit) and to adapt (edit, rewrite or remix) the work, with attribution to the original author for non-commercial purposes and if the work is edited or remixed, you may distribute the resulting work only under the same or similar licence to this one.
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/1327496
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