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

Nazif Alic, T. Daniel Andrews, Maria E. Giannakou, Irene Papatheodorou, Cathy Slack, Matthew P. Hoddinott, Helena M. Cochemé, Eugene F. Schuster, Janet M. Thornton, Linda Partridge

Research output: Contribution to journalArticle

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 dfoxo-independent 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.

LanguageEnglish
Article number502
Number of pages17
JournalMolecular Systems Biology
Volume7
Issue number1
DOIs
Publication statusPublished - 2011

Fingerprint

Insulin
transcriptomics
Diptera
topology
stress response
Genome
insulin
Genes
Topology
genomics
Target
Transcription factors
genome
Genomics
hormone receptors
Caenorhabditis elegans
somatomedins
Somatomedins
Transcription
Cytoplasmic and Nuclear Receptors

Bibliographical note

Molecular Systems Biology is an open-access journal published by European Molecular Biology Organization and Nature Publishing Group. Thiswork is licensed under a Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License.

Keywords

  • dFOXO
  • drosophila
  • insulin/insulin-like growth factor signaling
  • transcription

Cite this

Alic, N., Andrews, T. D., Giannakou, M. E., Papatheodorou, I., Slack, C., Hoddinott, M. P., ... Partridge, L. (2011). Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. 7(1), [502]. https://doi.org/10.1038/msb.2011.36
Alic, Nazif ; Andrews, T. Daniel ; Giannakou, Maria E. ; Papatheodorou, Irene ; Slack, Cathy ; Hoddinott, Matthew P. ; Cochemé, Helena M. ; Schuster, Eugene F. ; Thornton, Janet M. ; Partridge, Linda. / Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. 2011 ; Vol. 7, No. 1.
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Alic, N, Andrews, TD, Giannakou, ME, Papatheodorou, I, Slack, C, Hoddinott, MP, Cochemé, HM, Schuster, EF, Thornton, JM & Partridge, L 2011, 'Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling' vol. 7, no. 1, 502. https://doi.org/10.1038/msb.2011.36

Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. / Alic, Nazif; Andrews, T. Daniel; Giannakou, Maria E.; Papatheodorou, Irene; Slack, Cathy; Hoddinott, Matthew P.; Cochemé, Helena M.; Schuster, Eugene F.; Thornton, Janet M.; Partridge, Linda.

Vol. 7, No. 1, 502, 2011.

Research output: Contribution to journalArticle

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AU - Alic, Nazif

AU - Andrews, T. Daniel

AU - Giannakou, Maria E.

AU - Papatheodorou, Irene

AU - Slack, Cathy

AU - Hoddinott, Matthew P.

AU - Cochemé, Helena M.

AU - Schuster, Eugene F.

AU - Thornton, Janet M.

AU - Partridge, Linda

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