Journal
MOLECULAR SYSTEMS BIOLOGY
Volume 6, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/msb.2010.54
Keywords
aging; C. elegans; DAF-16/FoxO; DamID chromatin profiling; transcriptional networks
Categories
Funding
- Wellcome Trust [066750, 081394]
- European Commission [FP6-518230, LifeSpan 036894, LSHM-CT-2004-512020]
- Medical Research Council [G0800339]
- Ghent University [GOA 12050101]
- Fund for Scientific Research Flanders [G.0025.06]
- National Cancer Institute (NCI) [4 R33 CA097516-02]
- Medical Research Council [G0700729B, G0800339] Funding Source: researchfish
- MRC [G0800339] Funding Source: UKRI
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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. Molecular Systems Biology 6: 399; published online 10 August 2010; doi:10.1038/msb.2010.54 Subject Categories: metabolic and regulatory networks; chromatin and transcription
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