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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Animals
  • Binding Sites
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • 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


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Multiprotein Complexes
  • Transcription Factors
  • daf-16 protein, C elegans