DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity
Open accessAbstract
Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.
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DAF-16 interaction with SWI/SNF is required for its longevity-promoting action.
“This interaction is required for the longevity-promoting action of DAF-16 (Riedel et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Riedel et al., 2013
FOXO/DAF-16 and NRF/SKN-1 both promote changes in chromatin state and are sensitive to chromatin state.
“Importantly, both FOXO/DAF-16 and NRF/SKN-1 not only promote changes in chromatin state (Riedel et al., 2013; Zaret and Carroll, 2011; Zhang et al., 2006) but also are sensitive to them (Domcke et al., 2015; Eijkelenboom et al., 2013; Webb et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Riedel et al., 2013
In C. elegans, DAF-16 recruits SWI/SNF to activate age-related and stress-response genes including heat shock and oxidative stress genes.
“Furthermore, in C. elegans, DAF-16 recruits the chromatin remodeler SWI/SNF to activate expression of age-related and stress-response genes including heat shock proteins and oxidative stress-response genes (Riedel et al., 2013).”
From The Aging Epigenome (2016) · cites this paper as Riedel et al., 2013
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- Authors
- Riedel, C. G., Dowen, R. H., Lourenco, G. F., Kirienko, N. V., Heimbucher, T., West, J. A., Bowman, S. K., Kingston, R. E., Dillin, A., Asara, J. M., & Ruvkun, G.
- Affiliations
- Massachusetts General Hospital (US)
- Harvard University (US)
- Salk Institute for Biological Studies (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Ruvkun, Gary
- ORCID
- Venue
- Nature Cell Biology
- Published
- 2013-04-21
- Volume
- 15
- Issue
- 5
- Pages
- 491-501
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- PMC
- PMC3748955
- OpenAlex
- W2143810570
- Cited by
- 207
- References
- 54
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 10 · 2023: 13 · 2022: 11 · 2021: 13 · 2020: 14 · 2019: 16 · 2018: 21 · 2017: 15 · 2016: 27 · 2015: 20 · 2014: 18 · 2013: 5
- FWCI
- 10.44
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- National Institutes of Health (5f32ai100501-02)
- National Institute on Aging (R37AG014161, R01AG014161, AG016636, R56AG016636, AG014161, R01AG043184, R01AG016636)
- National Cancer Institute (P01CA120964, P30CA006516)
- National Institute of General Medical Sciences (GM048405, F32GM093491, R01GM048405, R37GM048405)
- National Institute of Allergy and Infectious Diseases (F32AI100501-01, F32 AI-100501)
- National Institute of Environmental Health Sciences (R01ES021667)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › FOXO transcription factor regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- DAF-16, FOXO transcription factors, transcriptional regulation, stress tolerance, longevity, lifespan regulation, dauer formation, Caenorhabditis elegans, protein complex formation
- MeSH terms
- Adaptation, Physiological, Animals, Binding Sites, Chromatography, Gel, Escherichia coli, Gene Expression Regulation, Longevity, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transcriptional Activation, Caenorhabditis elegans, Oxidative Stress, Caenorhabditis elegans Proteins, RNA Interference, Chromatin Assembly and Disassembly, Multiprotein Complexes, Forkhead Transcription Factors, Kaplan-Meier Estimate, Nucleotide Motifs
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