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Nat Cell Biol. 2013 May;15(5):491-501. doi: 10.1038/ncb2720. Epub 2013 Apr 21.

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

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1
Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

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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PMID:
23604319
PMCID:
PMC3748955
DOI:
10.1038/ncb2720
[Indexed for MEDLINE]
Free PMC Article

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