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Publication Detail

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

Authors: 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

Published In Nat Cell Biol, (2013 May)

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.

PubMed ID: 23604319 Exiting the NIEHS site

MeSH Terms: Adaptation, Physiological; Animals; Binding Sites; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism*; Caenorhabditis elegans/genetics; Caenorhabditis elegans/metabolism; Caenorhabditis elegans/physiology*; Chromatin Assembly and Disassembly*; Chromatography, Gel; Escherichia coli/genetics; Escherichia coli/metabolism; Forkhead Transcription Factors; Gene Expression Regulation; Kaplan-Meier Estimate; Longevity*; Multiprotein Complexes/genetics; Multiprotein Complexes/metabolism; Nucleotide Motifs; Oxidative Stress; Promoter Regions, Genetic; Protein Binding; RNA Interference; Transcription Factors/genetics; Transcription Factors/metabolism*; Transcriptional Activation

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