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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
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    References listed on IDEAS

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    1. 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.
    2. 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.
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