IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v8y2017i1d10.1038_s41467-017-01200-4.html
   My bibliography  Save this article

PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle

Author

Listed:
  • Christopher R. S. Banerji

    (New Hunt’s House, King’s College London, Guy’s Campus
    University College London
    University College London
    UCL Cancer Institute)

  • Maryna Panamarova

    (New Hunt’s House, King’s College London, Guy’s Campus)

  • Husam Hebaishi

    (New Hunt’s House, King’s College London, Guy’s Campus)

  • Robert B. White

    (New Hunt’s House, King’s College London, Guy’s Campus
    The University of Western Australia)

  • Frédéric Relaix

    (Paris Est-Creteil University, IMRB U955)

  • Simone Severini

    (University College London
    Institute of Natural Sciences)

  • Peter S. Zammit

    (New Hunt’s House, King’s College London, Guy’s Campus)

Abstract

Facioscapulohumeral muscular dystrophy (FSHD) is a prevalent, incurable myopathy, linked to hypomethylation of D4Z4 repeats on chromosome 4q causing expression of the DUX4 transcription factor. However, DUX4 is difficult to detect in FSHD muscle biopsies and it is debatable how robust changes in DUX4 target gene expression are as an FSHD biomarker. PAX7 is a master regulator of myogenesis that rescues DUX4-mediated apoptosis. Here, we show that suppression of PAX7 target genes is a hallmark of FSHD, and that it is as major a signature of FSHD muscle as DUX4 target gene expression. This is shown using meta-analysis of over six FSHD muscle biopsy gene expression studies, and validated by RNA-sequencing on FSHD patient-derived myoblasts. DUX4 also inhibits PAX7 from activating its transcriptional target genes and vice versa. Furthermore, PAX7 target gene repression can explain oxidative stress sensitivity and epigenetic changes in FSHD. Thus, PAX7 target gene repression is a hallmark of FSHD that should be considered in the investigation of FSHD pathology and therapy.

Suggested Citation

  • Christopher R. S. Banerji & Maryna Panamarova & Husam Hebaishi & Robert B. White & Frédéric Relaix & Simone Severini & Peter S. Zammit, 2017. "PAX7 target genes are globally repressed in facioscapulohumeral muscular dystrophy skeletal muscle," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01200-4
    DOI: 10.1038/s41467-017-01200-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-017-01200-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-017-01200-4?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
    ---><---

    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:8:y:2017:i:1:d:10.1038_s41467-017-01200-4. 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.