Aurora B and INCENP co-overexpression severely disrupts mitosis and distinctly modifies the global transcriptional landscape [ChIP-seq]
Aurora B kinase, as part of the chromosomal passenger complex (CPC), controls key processes during the cell cycle such as DNA compaction, genome partitioning or cytokinesis. Nonetheless, increased Aurora B levels are a potential threat for the cells and have been linked to different tumor types. We have carried out an exhaustive characterization of the global consequences of the overexpression of Aurora B and INCENP, the scaffold of the CPC and an activator of Aurora B kinase activity, in non-transformed human cells. Our data demonstrate, not only that an individual increase in the levels of Aurora B or INCENP have a different impact on the cells, but more importantly that their simultaneous overexpression stabilizes both CPC components, exacerbates Aurora B activity, severely impairs mitotic progression and chromosome dynamics, and has a distinctive and more dramatic effect on the transcriptional landscape of the cells. Overall design: In order to analyze the differential consequences of Aurora B and/or INCENP overexpression, we generated RPE-1 cells that conditionally expressed an extra copy of AURKB (AurkB), INCENP (INCENP),or a bi-cistronic construct that comprises both genes linked by a sequence encoding a P2A “self-cleaving” oligopeptide (Both), all under the control of the TET promoter. Chromatin immunoprecipitation DNA sequencing (ChIP-seq) for H3 Ser10 phosphorylation in each line, 32 hours after tetracycline addition to induce AurkB and/or INCENP overexpression. Two independent replicates were performed for each ChIP-seq experiment.