RRC ID 59373
Author Lin XX, Sen I, Janssens GE, Zhou X, Fonslow BR, Edgar D, Stroustrup N, Swoboda P, Yates JR 3rd, Ruvkun G, Riedel CG.
Title DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity.
Journal Nat Commun
Abstract The ability to perceive and respond to harmful conditions is crucial for the survival of any organism. The transcription factor DAF-16/FOXO is central to these responses, relaying distress signals into the expression of stress resistance and longevity promoting genes. However, its sufficiency in fulfilling this complex task has remained unclear. Using C. elegans, we show that DAF-16 does not function alone but as part of a transcriptional regulatory module, together with the transcription factor HLH-30/TFEB. Under harmful conditions, both transcription factors translocate into the nucleus, where they often form a complex, co-occupy target promoters, and co-regulate many target genes. Interestingly though, their synergy is stimulus-dependent: They rely on each other, functioning in the same pathway, to promote longevity or resistance to oxidative stress, but they elicit heat stress responses independently, and they even oppose each other during dauer formation. We propose that this module of DAF-16 and HLH-30 acts by combinatorial gene regulation to relay distress signals into the expression of specific target gene sets, ensuring optimal survival under each given threat.
Volume 9(1)
Pages 4400
Published 2018-10-23
DOI 10.1038/s41467-018-06624-0
PII 10.1038/s41467-018-06624-0
PMID 30353013
PMC PMC6199276
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Cell Nucleus / metabolism Epistasis, Genetic Forkhead Transcription Factors / metabolism* Gene Expression Regulation, Developmental Longevity / physiology* Models, Genetic Promoter Regions, Genetic Protein Binding Stress, Physiological*
IF 11.878
Times Cited 18
C.elegans tm1978