DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO

Schuster, Eugene, McElwee, Joshua J, Tullet, Jennifer M.A., Doonan, Ryan, Matthijssens, Filip, Reece-Hoyes, John S, Hope, Ian A, Vanfleteren, Jacques R, Thornton, Janet M, Gems, David and others. (2010) DamID in C. elegans reveals longevity-associated targets of DAF-16/FoxO. Molecular systems biology, 6 . ISSN 1744-4292. (doi:10.1038/msb.2010.54) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
http://dx.doi.org/10.1038/msb.2010.54

Abstract

Insulin/IGF-1 signaling controls metabolism, stress resistance and aging in Caenorhabditis elegans by regulating the activity of the DAF-16/FoxO transcription factor (TF). However, the function of DAF-16 and the topology of the transcriptional network that it crowns remain unclear. Using chromatin profiling by DNA adenine methyltransferase identification (DamID), we identified 907 genes that are bound by DAF-16. These were enriched for genes showing DAF-16-dependent upregulation in long-lived daf-2 insulin/IGF-1 receptor mutants (P=1.4e(-11)). Cross-referencing DAF-16 targets with these upregulated genes (daf-2 versus daf-16; daf-2) identified 65 genes that were DAF-16 regulatory targets. These 65 were enriched for signaling genes, including known determinants of longevity, but not for genes specifying somatic maintenance functions (e.g. detoxification, repair). This suggests that DAF-16 acts within a relatively small transcriptional subnetwork activating (but not suppressing) other regulators of stress resistance and aging, rather than directly regulating terminal effectors of longevity. For most genes bound by DAF-16::DAM, transcriptional regulation by DAF-16 was not detected, perhaps reflecting transcriptionally non-functional TF 'parking sites'. This study demonstrates the efficacy of DamID for chromatin profiling in C. elegans.

Item Type: Article
DOI/Identification number: 10.1038/msb.2010.54
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Jennifer Tullet
Date Deposited: 15 Oct 2014 11:01 UTC
Last Modified: 29 May 2019 13:10 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/43252 (The current URI for this page, for reference purposes)
Tullet, Jennifer M.A.: https://orcid.org/0000-0002-2037-526X
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