IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-24402-3.html
   My bibliography  Save this article

Reactivation of a developmentally silenced embryonic globin gene

Author

Listed:
  • Andrew J. King

    (University of Oxford)

  • Duantida Songdej

    (University of Oxford
    Mahidol University)

  • Damien J. Downes

    (University of Oxford)

  • Robert A. Beagrie

    (University of Oxford)

  • Siyu Liu

    (University of Oxford
    University of Oxford)

  • Megan Buckley

    (University of Oxford)

  • Peng Hua

    (University of Oxford)

  • Maria C. Suciu

    (University of Oxford)

  • A. Marieke Oudelaar

    (Max Planck Institute for Biophysical Chemistry)

  • Lars L. P. Hanssen

    (University of Oxford)

  • Danuta Jeziorska

    (University of Oxford)

  • Nigel Roberts

    (University of Oxford)

  • Stephanie J. Carpenter

    (University of Oxford)

  • Helena Francis

    (University of Oxford)

  • Jelena Telenius

    (University of Oxford
    University of Oxford)

  • Aude-Anais Olijnik

    (University of Oxford)

  • Jacqueline A. Sharpe

    (University of Oxford)

  • Jacqueline Sloane-Stanley

    (University of Oxford)

  • Jennifer Eglinton

    (John Radcliffe Hospital)

  • Mira T. Kassouf

    (University of Oxford)

  • Stuart H. Orkin

    (Harvard Medical School and Howard Hughes Medical Institute)

  • Len A. Pennacchio

    (Lawrence Berkeley National Laboratory
    University of California)

  • James O. J. Davies

    (University of Oxford)

  • Jim R. Hughes

    (University of Oxford
    University of Oxford)

  • Douglas R. Higgs

    (University of Oxford)

  • Christian Babbs

    (University of Oxford)

Abstract

The α- and β-globin loci harbor developmentally expressed genes, which are silenced throughout post-natal life. Reactivation of these genes may offer therapeutic approaches for the hemoglobinopathies, the most common single gene disorders. Here, we address mechanisms regulating the embryonically expressed α-like globin, termed ζ-globin. We show that in embryonic erythroid cells, the ζ-gene lies within a ~65 kb sub-TAD (topologically associating domain) of open, acetylated chromatin and interacts with the α-globin super-enhancer. By contrast, in adult erythroid cells, the ζ-gene is packaged within a small (~10 kb) sub-domain of hypoacetylated, facultative heterochromatin within the acetylated sub-TAD and that it no longer interacts with its enhancers. The ζ-gene can be partially re-activated by acetylation and inhibition of histone de-acetylases. In addition to suggesting therapies for severe α-thalassemia, these findings illustrate the general principles by which reactivation of developmental genes may rescue abnormalities arising from mutations in their adult paralogues.

Suggested Citation

  • Andrew J. King & Duantida Songdej & Damien J. Downes & Robert A. Beagrie & Siyu Liu & Megan Buckley & Peng Hua & Maria C. Suciu & A. Marieke Oudelaar & Lars L. P. Hanssen & Danuta Jeziorska & Nigel Ro, 2021. "Reactivation of a developmentally silenced embryonic globin gene," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24402-3
    DOI: 10.1038/s41467-021-24402-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-24402-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-24402-3?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. Jingxuan Xu & Xiang Xu & Dandan Huang & Yawen Luo & Lin Lin & Xuemei Bai & Yang Zheng & Qian Yang & Yu Cheng & An Huang & Jingyi Shi & Xiaochen Bo & Jin Gu & Hebing Chen, 2024. "A comprehensive benchmarking with interpretation and operational guidance for the hierarchy of topologically associating domains," Nature Communications, Nature, vol. 15(1), pages 1-19, 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:12:y:2021:i:1:d:10.1038_s41467-021-24402-3. 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.