IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45353-5.html
   My bibliography  Save this article

G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis

Author

Listed:
  • Wenmeng Wang

    (Northeast Forestry University)

  • Dangdang Li

    (Northeast Forestry University)

  • Qingqing Xu

    (Northeast Forestry University)

  • Jiahui Cheng

    (Northeast Forestry University)

  • Zhiwei Yu

    (Harbin Medical University Cancer Hospital)

  • Guangyue Li

    (Northeast Forestry University)

  • Shiyao Qiao

    (Northeast Forestry University)

  • Jiasong Pan

    (Northeast Forestry University)

  • Hao Wang

    (Northeast Forestry University)

  • Jinming Shi

    (Northeast Forestry University)

  • Tongsen Zheng

    (Harbin Medical University Cancer Hospital
    Key Laboratory of Molecular Oncology of Heilongjiang Province)

  • Guangchao Sui

    (Northeast Forestry University)

Abstract

G-quadruplexes (G4s) can recruit transcription factors to activate gene expression, but detailed mechanisms remain enigmatic. Here, we demonstrate that G4s in the CCND1 promoter propel the motility in MAZ phase-separated condensates and subsequently activate CCND1 transcription. Zinc finger (ZF) 2 of MAZ is a responsible for G4 binding, while ZF3-5, but not a highly disordered region, is critical for MAZ condensation. MAZ nuclear puncta overlaps with signals of G4s and various coactivators including BRD4, MED1, CDK9 and active RNA polymerase II, as well as gene activation histone markers. MAZ mutants lacking either G4 binding or phase separation ability did not form nuclear puncta, and showed deficiencies in promoting hepatocellular carcinoma cell proliferation and xenograft tumor formation. Overall, we unveiled that G4s recruit MAZ to the CCND1 promoter and facilitate the motility in MAZ condensates that compartmentalize coactivators to activate CCND1 expression and subsequently exacerbate hepatocarcinogenesis.

Suggested Citation

  • Wenmeng Wang & Dangdang Li & Qingqing Xu & Jiahui Cheng & Zhiwei Yu & Guangyue Li & Shiyao Qiao & Jiasong Pan & Hao Wang & Jinming Shi & Tongsen Zheng & Guangchao Sui, 2024. "G-quadruplexes promote the motility in MAZ phase-separated condensates to activate CCND1 expression and contribute to hepatocarcinogenesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45353-5
    DOI: 10.1038/s41467-024-45353-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45353-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45353-5?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. Mahmoud M. Elguindy & Joshua T. Mendell, 2021. "NORAD-induced Pumilio phase separation is required for genome stability," Nature, Nature, vol. 595(7866), pages 303-308, July.
    2. Rajesh Sharma & Kyoung-Jae Choi & My Diem Quan & Sonum Sharma & Banumathi Sankaran & Hyekyung Park & Anel LaGrone & Jean J. Kim & Kevin R. MacKenzie & Allan Chris M. Ferreon & Choel Kim & Josephine C., 2021. "Liquid condensation of reprogramming factor KLF4 with DNA provides a mechanism for chromatin organization," Nature Communications, Nature, vol. 12(1), pages 1-17, 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. Tuan Nguyen & Sai Li & Jeremy T-H Chang & John W. Watters & Htet Ng & Adewola Osunsade & Yael David & Shixin Liu, 2022. "Chromatin sequesters pioneer transcription factor Sox2 from exerting force on DNA," Nature Communications, Nature, vol. 13(1), pages 1-11, 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:15:y:2024:i:1:d:10.1038_s41467-024-45353-5. 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.