Abstract
The evolutionary conserved NSL complex is a prominent epigenetic regulator controlling expression of thousands of genes. Here we uncover a novel function of the NSL complex members in mitosis. As the cell enters mitosis, KANSL1 and KANSL3 undergo a marked relocalisation from the chromatin to the mitotic spindle. By stabilizing microtubule minus ends in a RanGTP-dependent manner, they are essential for spindle assembly and chromosome segregation. Moreover, we identify KANSL3 as a microtubule minus-end-binding protein, revealing a new class of mitosis-specific microtubule minus-end regulators. By adopting distinct functions in interphase and mitosis, KANSL proteins provide a link to coordinate the tasks of faithful expression and inheritance of the genome during different phases of the cell cycle.
Highlights
The evolutionary conserved NSL complex is a prominent epigenetic regulator controlling expression of thousands of genes
Co-immunoprecipitation experiments in nocodazolesynchronized HeLa cells further showed that KANSL proteins were able to interact efficiently in mitosis as they do in interphase cells (Supplementary Fig. 1b)
Knockdown of KANSL1 or KANSL3 resulted in marked mitotic defects, the most prevalent of which was a prolonged arrest of cells in a prometaphase-like state (Fig. 1b; Supplementary Fig. 1d; Supplementary Movies 1–3)
Summary
The evolutionary conserved NSL complex is a prominent epigenetic regulator controlling expression of thousands of genes. Drosophila KANSL null mutants die latest in larval stages, and likely only survive far due to maternal contribution[6] Misregulation of these proteins is associated with diverse disease states in humans. Some nuclear proteins are known to play an essential role in the assembly of the mitotic spindle, by promoting microtubule nucleation and stabilization at the vicinity of the chromosomes[15] This process is dependent on the small GTPase Ran, whose active GTP-bound form is concentrated around the mitotic chromatin[16]. A number of RanGTP-regulated spindle assembly factors have been identified so far[17,18], including Imitation Switch (ISWI), which functions as a nucleosome remodeler in interphase[19] It remains unclear how many other epigenetic complexes may have functions in mitosis not related to chromatin states or gene expression
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