title: DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.
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.
authors.affiliation: Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
authors.forename: Christian G
authors.initials: CG
authors.lastname: Riedel
authors.forename: Robert H
authors.initials: RH
authors.lastname: Dowen
authors.forename: Guinevere F
authors.initials: GF
authors.lastname: Lourenco
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Kirienko
authors.forename: Thomas
authors.initials: T
authors.lastname: Heimbucher
authors.forename: Jason A
authors.initials: JA
authors.lastname: West
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Bowman
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kingston
authors.forename: Andrew
authors.initials: A
authors.lastname: Dillin
authors.forename: John M
authors.initials: JM
authors.lastname: Asara
authors.forename: Gary
authors.initials: G
authors.lastname: Ruvkun
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002850:Chromatography, Gel; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors; D005786:Gene Expression Regulation; D053208:Kaplan-Meier Estimate; D008136:Longevity; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D059372:Nucleotide Motifs; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D046912:Multiprotein Complexes; D014157:Transcription Factors; C108831:daf-16 protein, C elegans