Cited by 207FOXO transcription factor regulationGenetics, Aging, and Longevity in Model OrganismsChromatin Remodeling and Cancer

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DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

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Riedel, Christian G., Dowen, Robert H., Lourenco, Guinevere F., Kirienko, Natalia V., Heimbucher, Thomas, West, Jason A., Bowman, Sarah K., Kingston, Robert E., Dillin, Andrew, Asara, John M., Ruvkun, Gary·2013·Nature Cell Biology

DOI 10.1038/ncb2720PMC PMC3748955

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Abstract

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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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: Riedel, Christian G.
Dowen, Robert H.
Lourenco, Guinevere F.
Kirienko, Natalia V.
Heimbucher, Thomas
West, Jason A.
Kingston, Robert E.
Dillin, Andrew
Asara, John M.
Ruvkun, Gary
Venue: Nature Cell Biology
Publisher: Springer Science and Business Media LLC
Published: 2013-04-21
Volume: 15
Issue: 5
Pages: 491-501
ISSN: 1465-7392 (ISSN-L)
1476-4679
DOI: 10.1038/ncb2720
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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DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

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