IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32408-8.html
   My bibliography  Save this article

Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities

Author

Listed:
  • Pedro B. Pinto

    (Centre for Organismal Studies (COS) Heidelberg
    Universite Claude Bernard Lyon 1)

  • Katrin Domsch

    (Centre for Organismal Studies (COS) Heidelberg)

  • Xuefan Gao

    (Centre for Organismal Studies (COS) Heidelberg)

  • Michaela Wölk

    (Centre for Organismal Studies (COS) Heidelberg
    Friedrich Miescher Institute for Biomedical Research (FMI))

  • Julie Carnesecchi

    (Centre for Organismal Studies (COS) Heidelberg
    Universite Claude Bernard Lyon 1)

  • Ingrid Lohmann

    (Centre for Organismal Studies (COS) Heidelberg)

Abstract

Hox proteins have similar binding specificities in vitro, yet they control different morphologies in vivo. This paradox has been partially solved with the identification of Hox low-affinity binding sites. However, anterior Hox proteins are more promiscuous than posterior Hox proteins, raising the question how anterior Hox proteins achieve specificity. We use the AP2x enhancer, which is activated in the maxillary head segment by the Hox TF Deformed (Dfd). This enhancer lacks canonical Dfd-Exd sites but contains several predicted low-affinity sites. Unexpectedly, these sites are strongly bound by Dfd-Exd complexes and their conversion into optimal Dfd-Exd sites results only in a modest increase in binding strength. These small variations in affinity change the sensitivity of the enhancer to different Dfd levels, resulting in perturbed AP-2 expression and maxillary morphogenesis. Thus, Hox-regulated morphogenesis seems to result from the co-evolution of Hox binding affinity and Hox dosage for precise target gene regulation.

Suggested Citation

  • Pedro B. Pinto & Katrin Domsch & Xuefan Gao & Michaela Wölk & Julie Carnesecchi & Ingrid Lohmann, 2022. "Specificity of the Hox member Deformed is determined by transcription factor levels and binding site affinities," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32408-8
    DOI: 10.1038/s41467-022-32408-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32408-8
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-32408-8?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
    ---><---

    References listed on IDEAS

    as
    1. Siqian Feng & Chaitanya Rastogi & Ryan Loker & William J. Glassford & H. Tomas Rube & Harmen J. Bussemaker & Richard S. Mann, 2022. "Transcription factor paralogs orchestrate alternative gene regulatory networks by context-dependent cooperation with multiple cofactors," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Ashton S. Holub & Sarah G. Choudury & Ekaterina P. Andrianova & Courtney E. Dresden & Ricardo Urquidi Camacho & Igor B. Zhulin & Aman Y. Husbands, 2024. "START domains generate paralog-specific regulons from a single network architecture," Nature Communications, Nature, vol. 15(1), pages 1-18, 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:13:y:2022:i:1:d:10.1038_s41467-022-32408-8. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.