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PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites

Author

Listed:
  • Andrew Dimond

    (Hammersmith Hospital Campus
    University of Oxford)

  • Do Hyeon Gim

    (Hammersmith Hospital Campus)

  • Elizabeth Ing-Simmons

    (Hammersmith Hospital Campus)

  • Chad Whilding

    (Hammersmith Hospital Campus)

  • Holger B. Kramer

    (Cambridge Biomedical Campus)

  • Dounia Djeghloul

    (Hammersmith Hospital Campus
    University of Oxford)

  • Alex Montoya

    (Hammersmith Hospital Campus)

  • Bhavik Patel

    (Hammersmith Hospital Campus)

  • Sherry Cheriyamkunnel

    (Hammersmith Hospital Campus
    University of Oxford)

  • Karen E. Brown

    (Hammersmith Hospital Campus
    University of Oxford)

  • Pavel V. Shliaha

    (Hammersmith Hospital Campus)

  • Juan M. Vaquerizas

    (Hammersmith Hospital Campus)

  • Matthias Merkenschlager

    (Hammersmith Hospital Campus)

  • Amanda G. Fisher

    (Hammersmith Hospital Campus
    University of Oxford)

Abstract

PBK/TOPK is a mitotic kinase implicated in haematological and non-haematological cancers. Here we show that the key haemopoietic regulators Ikaros and Aiolos require PBK-mediated phosphorylation to dissociate from chromosomes in mitosis. Eviction of Ikaros is rapidly reversed by addition of the PBK-inhibitor OTS514, revealing dynamic regulation by kinase and phosphatase activities. To identify more PBK targets, we analysed loss of mitotic phosphorylation events in Pbk–/– preB cells and performed proteomic comparisons on isolated mitotic chromosomes. Among a large pool of C2H2-zinc finger targets, PBK is essential for evicting the CCCTC-binding protein CTCF and zinc finger proteins encoded by Ikzf1, Ikzf3, Znf131 and Zbtb11. PBK-deficient cells were able to divide but showed altered chromatin accessibility and nucleosome positioning consistent with CTCF retention. Our studies reveal that PBK controls the dissociation of selected factors from condensing mitotic chromosomes and contributes to their compaction.

Suggested Citation

  • Andrew Dimond & Do Hyeon Gim & Elizabeth Ing-Simmons & Chad Whilding & Holger B. Kramer & Dounia Djeghloul & Alex Montoya & Bhavik Patel & Sherry Cheriyamkunnel & Karen E. Brown & Pavel V. Shliaha & J, 2025. "PBK/TOPK mediates Ikaros, Aiolos and CTCF displacement from mitotic chromosomes and alters chromatin accessibility at selected C2H2-zinc finger protein binding sites," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63740-4
    DOI: 10.1038/s41467-025-63740-4
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