IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06624-0.html
   My bibliography  Save this article

DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity

Author

Listed:
  • Xin-Xuan Lin

    (Karolinska Institute
    Karolinska Institute
    University of Groningen, Antonius Deusinglaan, 1)

  • Ilke Sen

    (Karolinska Institute
    Karolinska Institute
    University of Groningen, Antonius Deusinglaan, 1)

  • Georges E. Janssens

    (Karolinska Institute)

  • Xin Zhou

    (Karolinska Institute
    Karolinska Institute)

  • Bryan R. Fonslow

    (The Scripps Research Institute)

  • Daniel Edgar

    (Karolinska Institute
    Karolinska Institute)

  • Nicholas Stroustrup

    (The Barcelona Institute of Science and Technology
    Universitat Pompeu Fabra (UPF)
    Harvard Medical School)

  • Peter Swoboda

    (Karolinska Institute)

  • John R. Yates

    (The Scripps Research Institute)

  • Gary Ruvkun

    (Massachusetts General Hospital
    Harvard Medical School)

  • Christian G. Riedel

    (Karolinska Institute
    Karolinska Institute
    University of Groningen, Antonius Deusinglaan, 1)

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.

Suggested Citation

  • Xin-Xuan Lin & Ilke Sen & Georges E. Janssens & Xin Zhou & Bryan R. Fonslow & Daniel Edgar & Nicholas Stroustrup & Peter Swoboda & John R. Yates & Gary Ruvkun & Christian G. Riedel, 2018. "DAF-16/FOXO and HLH-30/TFEB function as combinatorial transcription factors to promote stress resistance and longevity," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06624-0
    DOI: 10.1038/s41467-018-06624-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06624-0
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-018-06624-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Elite Possik & Laura-Lee Klein & Perla Sanjab & Ruyuan Zhu & Laurence Côté & Ying Bai & Dongwei Zhang & Howard Sun & Anfal Al-Mass & Abel Oppong & Rasheed Ahmad & Alex Parker & S.R. Murthy Madiraju & , 2023. "Glycerol 3-phosphate phosphatase/PGPH-2 counters metabolic stress and promotes healthy aging via a glycogen sensing-AMPK-HLH-30-autophagy axis in C. elegans," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Ian F. Price & Jillian A. Wagner & Benjamin Pastore & Hannah L. Hertz & Wen Tang, 2023. "C. elegans germ granules sculpt both germline and somatic RNAome," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06624-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.