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bioRxiv · 10.1101/2025.10.05.680587

Dual pathways via CENP-C and Mis18C recruit HJURP for CENP-A deposition into vertebrate centromeres

Hori, T.·Mahana, Y.·Ariyoshi, M.·Fukagawa, T.
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Abstract

Centromere position is specified and maintained by sequence-independent epigenetic mechanisms in vertebrate cells, with the incorporation of the centromere-specific histone H3 variant CENP-A into chromatin being a key event for centromere specification. Although many models for CENP-A incorporation have been proposed, much remains unknown. In this study, we reveal that the CENP-A chaperone HJURP directly binds to the C-terminal domain of chicken CENP-C in vitro and that this interaction is essential for new CENP-A incorporation in chicken DT40 cells. While existing models have suggested that HJURP is recruited by the Mis18 complex (Mis18C), here, we propose that CENP-C and Mis18C provide dual recruitment pathways for HJURP localization to centromeres in DT40 cells. We demonstrate that both HJURP localization and new CENP-A incorporation are completely abolished in Mis18C knockout cells expressing an HJURP mutant lacking CENP-C binding ability. Furthermore, co-immunoprecipitation experiments reveal that CENP-C, HJURP and Mis18C form a tight association in the chromatin fraction. These two pathways are critical for robust CENP-A incorporation to maintain centromere position in vertebrate cells.

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Hori, T., Mahana, Y., Ariyoshi, M., Fukagawa, T.. 2025-10-06. Dual pathways via CENP-C and Mis18C recruit HJURP for CENP-A deposition into vertebrate centromeres. https://doi.org/10.1101/2025.10.05.680587

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