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

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, Juan M. Vaquerizas, Matthias Merkenschlager and Amanda G. Fisher ()
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Andrew Dimond: Hammersmith Hospital Campus
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
Alex Montoya: Hammersmith Hospital Campus
Bhavik Patel: Hammersmith Hospital Campus
Sherry Cheriyamkunnel: Hammersmith Hospital Campus
Karen E. Brown: Hammersmith Hospital Campus
Pavel V. Shliaha: Hammersmith Hospital Campus
Juan M. Vaquerizas: Hammersmith Hospital Campus
Matthias Merkenschlager: Hammersmith Hospital Campus
Amanda G. Fisher: Hammersmith Hospital Campus

Nature Communications, 2025, vol. 16, issue 1, 1-20

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63740-4

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