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.
Highlights
The ability to perceive and respond to harmful conditions is crucial for the survival of any organism
In a previous search for binding partners of DAF-16/FOXO, we conducted large-scale purifications of GFP-tagged DAF-16 from whole C. elegans, using three different genetic backgrounds: wild type, daf-2(e1370), and daf-18(mg198)[7]
Being interested in other transcription factors that DAF-16 might closely synergize with, we focused on the transcription factor most abundant in DAF-16 purifications: the conserved helix-loop-helix transcription factor HLH-30 (Fig. 1a)
Summary
The ability to perceive and respond to harmful conditions is crucial for the survival of any organism. 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. Common strategy for most of these pathways is the relay of distress signals into transcriptional changes, in particular the induction of genes that promote stress resistance, slow down the aging process, and infer longevity, which improves the organisms’ chances of survival Careful coordination of these signaling pathways and their transcriptional outcomes is crucial, so that responses are both effective for their task and energy efficient, making best use of an organism’s resources. Given the complexity of the task to relay nature’s diverse distress signals into customized responses, the question arises whether DAF-16/FOXO alone is sufficient to fulfill it, or whether there exist other transcription factors with complementary functions that DAF-16/FOXO must synergize with
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
