IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-54824-8.html
   My bibliography  Save this article

SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers

Author

Listed:
  • Mahnaz Hosseinpour

    (Monash University
    Monash University
    The University of Melbourne)

  • Xinqi Xi

    (Monash University)

  • Ling Liu

    (Monash University)

  • Luis Malaver-Ortega

    (Monash University)

  • Laura Perlaza-Jimenez

    (Monash University)

  • Jihoon E. Joo

    (The University of Melbourne)

  • Harrison M. York

    (Monash University)

  • Jonathan Beesley

    (QIMR Berghofer Medical Research Institute)

  • C. Elizabeth Caldon

    (Garvan Institute of Medical Research)

  • Pierre-Antoine Dugué

    (Monash University
    Cancer Council Victoria
    The University of Melbourne)

  • James G. Dowty

    (The University of Melbourne)

  • Senthil Arumugam

    (Monash University
    Monash University)

  • Melissa C. Southey

    (Monash University
    The University of Melbourne
    Cancer Council Victoria)

  • Joseph Rosenbluh

    (Monash University
    Monash University)

Abstract

DNA methylation is an epigenetic mark that plays a critical role in regulating gene expression. DNA methyltransferase (DNMT) inhibitors, inhibit global DNA methylation and have been a key tool in studies of DNA methylation. A major bottleneck is the lack of tools to induce global DNA methylation. Here, we engineered a CRISPR based approach, that we initially designed, to enable site-specific DNA methylation. Using the synergistic activation mediator (SAM) system, we unexpectedly find that regardless of the targeted sequence any sgRNA induces global genome-wide DNA methylation. We term this method SAM-DNMT3A and show that induction of global DNA methylation is a unique vulnerability in ER-positive breast cancer suggesting a therapeutic approach. Our findings highlight the need of caution when using CRISPR based approaches for inducing DNA methylation and demonstrate a method for global induction of DNA methylation.

Suggested Citation

  • Mahnaz Hosseinpour & Xinqi Xi & Ling Liu & Luis Malaver-Ortega & Laura Perlaza-Jimenez & Jihoon E. Joo & Harrison M. York & Jonathan Beesley & C. Elizabeth Caldon & Pierre-Antoine Dugué & James G. Dow, 2024. "SAM-DNMT3A, a strategy for induction of genome-wide DNA methylation, identifies DNA methylation as a vulnerability in ER-positive breast cancers," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54824-8
    DOI: 10.1038/s41467-024-54824-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-54824-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-54824-8?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
    ---><---

    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:15:y:2024:i:1:d:10.1038_s41467-024-54824-8. 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.

    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.