Condensin association with histone H2A shapes mitotic chromosomes

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Abstract

Chromosome structure is dynamically regulated during cell division, and this regulation is dependent, in part, on condensin. The localization of condensin at chromosome arms is crucial for chromosome partitioning during anaphase. Condensin is also enriched at kinetochores but its precise role and loading machinery remain unclear. Here we show that fission yeast (Schizosaccharomyces pombe) kinetochore proteins Pcs1 and Mde4—homologues of budding yeast (Saccharomyces cerevisiae) monopolin subunits and known to prevent merotelic kinetochore orientation—act as a condensin ‘recruiter’ at kinetochores, and that condensin itself may act to clamp microtubule binding sites during metaphase. In addition to the regional recruitment factors, overall condensin association with chromatin is governed by the chromosomal passenger kinase Aurora B. Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin ‘receptors’ of condensin. Condensin phosphorylation and its deposition onto chromosome arms reach a peak during anaphase, when Aurora B kinase relocates from centromeres to the spindle midzone, where the separating chromosome arms are positioned. Our results elucidate the molecular basis for the spatiotemporal regulation of mitotic chromosome architecture, which is crucial for chromosome partitioning.

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Figure 1: Dissection of condensin function at the kinetochore and chromosome arm.
Figure 2: Phosphorylation of condensin by Aurora B is required for chromatin association.
Figure 3: Chromatin association of human condensin I is also regulated by Aurora-B-dependent phosphorylation.
Figure 4: H2A and H2A.Z act as a chromatin receptor of condensin.
Figure 5: Spatiotemporal regulation of condensin localization by Aurora B.

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  • 12 June 2011

    The Supplementary Information PDF was replaced.

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Acknowledgements

We thank S. Hauf for critically reading the manuscript and K.-i. Noma, T. Hirano and the Yeast Genetic Resource Center (YGRC) for yeast strains or reagents. We also thank S. Hauf and M. Yanagida for communicating unpublished results, and all the members of our laboratory for their support and discussion. This work was supported in part by Global COE Program (Integrative Life Science Based on the Study of Biosignaling Mechanisms) (to K.T. and H.S.), Special Coordination Funds for Promoting Science and Technology (to T.S.) and a Grant-in-Aid for Specially Promoted Research, MEXT, Japan (to Y.W.).

Author information

K.T., supported by T.S., performed most of the experiments using fission yeast cells and proteins. H.S. performed all experiments using human cells or proteins. Experimental design and interpretation of data were conducted by all authors. Y.W. supervised the project and K.T. and Y.W. wrote the paper.

Correspondence to Yoshinori Watanabe.

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Tada, K., Susumu, H., Sakuno, T. et al. Condensin association with histone H2A shapes mitotic chromosomes. Nature 474, 477–483 (2011) doi:10.1038/nature10179

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