Abstract
The centromere of a chromosome is composed mainly of two domains, a kinetochore assembling core centromere and peri-centromeric heterochromatin regions1,2. The crucial role of centromeric heterochromatin is still unknown, because even in simpler unicellular organisms such as the fission yeast Schizosaccharomyces pombe, the heterochromatin protein Swi6 (HP1 homologue) has several functions at centromeres, including silencing gene expression and recombination, enriching cohesin, promoting kinetochore assembly, and, ultimately, preventing erroneous microtubule attachment to the kinetochores1,3,4,5,6. Here we show that the requirement of heterochromatin for mitotic chromosome segregation is largely replaced by forcibly enriching cohesin at centromeres in fission yeast. However, this enrichment of cohesin is not sufficient to replace the meiotic requirement for heterochromatin. We find that the heterochromatin protein Swi6 associates directly with meiosis-specific shugoshin Sgo1, a protector of cohesin at centromeres. A point mutation of Sgo1 (V242E), which abolishes the interaction with Swi6, impairs the centromeric localization and function of Sgo1. The forced centromeric localization of Sgo1 restores proper meiotic chromosome segregation in swi6Δ cells. We also show that the direct link between HP1 and shugoshin is conserved in human cells. Taken together, our findings suggest that the recruitment of shugoshin is the important primary role for centromeric heterochromatin in ensuring eukaryotic chromosome segregation.
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Acknowledgements
We thank S. Hauf for reading the manuscript critically; R. Allshire, S. Grewal and the Yeast Genetic Resource Center (YGRC) for yeast strains; J.-i. Nakayama for Swi6 antibody; and all the members of our laboratory for their valuable support and discussion. This work was supported in part by the Global COE programme (Integrative life Science Based on the Study of Biosignaling Mechanisms), MEXT, Japan, the Toray Science Foundation (to Y.W.), Special Coordination Funds for Promoting Science and Technology (to T.S.) and Grants-in-Aid for Research on Advanced Medical Technology, Ministry of Health, Labour and Welfare (to M.S.) and for Specially Promoted Research, MEXT, Japan (to Y.W.).
Author Contributions Experiments in Fig. 1 were performed mainly by T.S., those in Figs 2, 3 and 4a–c by Y.Y., and those in Fig. 4d–f by M.S. Experimental design and interpretation of data were conducted by all authors. Y.W. planned the project and wrote the paper with input from co-authors.
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Yamagishi, Y., Sakuno, T., Shimura, M. et al. Heterochromatin links to centromeric protection by recruiting shugoshin. Nature 455, 251–255 (2008). https://doi.org/10.1038/nature07217
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DOI: https://doi.org/10.1038/nature07217
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