DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity
Riedel, Christian G.
Lourenco, Guinevere F.
West, Jason A.
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CitationRiedel, C. G., R. H. Dowen, G. F. Lourenco, N. V. Kirienko, T. Heimbucher, J. A. West, S. K. Bowman, et al. 2013. “DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.” Nature cell biology 15 (5): 491-501. doi:10.1038/ncb2720. http://dx.doi.org/10.1038/ncb2720.
AbstractOrganisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The transcription factor DAF-16/FOXO is 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 (RNAi) 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 colocalize 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, in order to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role of SWI/SNF for DAF-16/FOXO-mediated processes, i.e. 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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