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A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival

Author

Listed:
  • Samuel Abassah-Oppong

    (University of Calgary, 2500 University Drive N.W.
    Fort Hays State University)

  • Matteo Zoia

    (University of Bern)

  • Brandon J. Mannion

    (Lawrence Berkeley National Laboratory
    University of California)

  • Raquel Rouco

    (University of Geneva)

  • Virginie Tissières

    (University of Bern
    CSIC-Universidad Pablo de Olavide-Junta de Andalucía
    Bern University Hospital)

  • Cailyn H. Spurrell

    (Lawrence Berkeley National Laboratory)

  • Virginia Roland

    (University of Bern)

  • Fabrice Darbellay

    (Lawrence Berkeley National Laboratory
    University of Geneva)

  • Anja Itum

    (University of Calgary, 2500 University Drive N.W.)

  • Julie Gamart

    (University of Bern
    Bern University Hospital)

  • Tabitha A. Festa-Daroux

    (University of Calgary, 2500 University Drive N.W.)

  • Carly S. Sullivan

    (University of Calgary, 2500 University Drive N.W.)

  • Michael Kosicki

    (Lawrence Berkeley National Laboratory)

  • Eddie Rodríguez-Carballo

    (University of Geneva
    University of Geneva)

  • Yoko Fukuda-Yuzawa

    (Lawrence Berkeley National Laboratory)

  • Riana D. Hunter

    (Lawrence Berkeley National Laboratory)

  • Catherine S. Novak

    (Lawrence Berkeley National Laboratory)

  • Ingrid Plajzer-Frick

    (Lawrence Berkeley National Laboratory)

  • Stella Tran

    (Lawrence Berkeley National Laboratory)

  • Jennifer A. Akiyama

    (Lawrence Berkeley National Laboratory)

  • Diane E. Dickel

    (Lawrence Berkeley National Laboratory)

  • Javier Lopez-Rios

    (CSIC-Universidad Pablo de Olavide-Junta de Andalucía
    Universidad Loyola Andalucía)

  • Iros Barozzi

    (Lawrence Berkeley National Laboratory
    Medical University of Vienna)

  • Guillaume Andrey

    (University of Geneva)

  • Axel Visel

    (Lawrence Berkeley National Laboratory
    Lawrence Berkeley National Laboratory
    University of California, Merced)

  • Len A. Pennacchio

    (Lawrence Berkeley National Laboratory
    University of California
    Lawrence Berkeley National Laboratory)

  • John Cobb

    (University of Calgary, 2500 University Drive N.W.)

  • Marco Osterwalder

    (University of Bern
    Lawrence Berkeley National Laboratory
    Bern University Hospital)

Abstract

Approximately a quarter of the human genome consists of gene deserts, large regions devoid of genes often located adjacent to developmental genes and thought to contribute to their regulation. However, defining the regulatory functions embedded within these deserts is challenging due to their large size. Here, we explore the cis-regulatory architecture of a gene desert flanking the Shox2 gene, which encodes a transcription factor indispensable for proximal limb, craniofacial, and cardiac pacemaker development. We identify the gene desert as a regulatory hub containing more than 15 distinct enhancers recapitulating anatomical subdomains of Shox2 expression. Ablation of the gene desert leads to embryonic lethality due to Shox2 depletion in the cardiac sinus venosus, caused in part by the loss of a specific distal enhancer. The gene desert is also required for stylopod morphogenesis, mediated via distributed proximal limb enhancers. In summary, our study establishes a multi-layered role of the Shox2 gene desert in orchestrating pleiotropic developmental expression through modular arrangement and coordinated dynamics of tissue-specific enhancers.

Suggested Citation

  • Samuel Abassah-Oppong & Matteo Zoia & Brandon J. Mannion & Raquel Rouco & Virginie Tissières & Cailyn H. Spurrell & Virginia Roland & Fabrice Darbellay & Anja Itum & Julie Gamart & Tabitha A. Festa-Da, 2024. "A gene desert required for regulatory control of pleiotropic Shox2 expression and embryonic survival," Nature Communications, Nature, vol. 15(1), pages 1-24, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53009-7
    DOI: 10.1038/s41467-024-53009-7
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    References listed on IDEAS

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