Alic, Nazif, Andrews, T. Daniel, Giannakou, Maria E., Papatheodorou, Irene, Slack, Cathy, Hoddinott, Matthew P., Cochemé, Helena M., Schuster, Eugene F., Thornton, Janet M. and Partridge, Linda (2011). Genome-wide dFOXO targets and topology of the transcriptomic response to stress and insulin signalling. Molecular Systems Biology, 7 (1),
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.
Publication DOI: | https://doi.org/10.1038/msb.2011.36 |
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Divisions: | College of Health & Life Sciences College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research |
Additional Information: | 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. |
Uncontrolled Keywords: | dFOXO,drosophila,insulin/insulin-like growth factor signaling,transcription,General Medicine,Information Systems,General Immunology and Microbiology,General Biochemistry,Genetics and Molecular Biology,General Agricultural and Biological Sciences,Computational Theory and Mathematics,Applied Mathematics |
Publication ISSN: | 1744-4292 |
Last Modified: | 05 Dec 2024 08:09 |
Date Deposited: | 03 May 2017 12:15 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) |
PURE Output Type: | Article |
Published Date: | 2011 |
Authors: |
Alic, Nazif
Andrews, T. Daniel Giannakou, Maria E. Papatheodorou, Irene Slack, Cathy ( 0000-0002-7949-4079) Hoddinott, Matthew P. Cochemé, Helena M. Schuster, Eugene F. Thornton, Janet M. Partridge, Linda |
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