Molecular basis of CENP-C association with the CENP-A nucleosome at yeast centromeres
- Hua Xiao1,
- Feng Wang1,9,
- Jan Wisniewski2,9,
- Alexey K. Shaytan3,9,
- Rodolfo Ghirlando4,
- Peter C. FitzGerald5,
- Yingzi Huang1,8,
- Debbie Wei1,
- Shipeng Li1,
- David Landsman3,
- Anna R. Panchenko3 and
- Carl Wu1,2,6,7
- 1Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 2Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA;
- 3National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20894, USA;
- 4Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 5Genome Analysis Unit, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
- 6Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA;
- 7Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
- Corresponding authors: wuc{at}jhu.edu, xiaoh{at}mail.nih.gov
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↵9 These authors contributed equally to this work.
Abstract
Histone CENP-A-containing nucleosomes play an important role in nucleating kinetochores at centromeres for chromosome segregation. However, the molecular mechanisms by which CENP-A nucleosomes engage with kinetochore proteins are not well understood. Here, we report the finding of a new function for the budding yeast Cse4/CENP-A histone-fold domain interacting with inner kinetochore protein Mif2/CENP-C. Strikingly, we also discovered that AT-rich centromere DNA has an important role for Mif2 recruitment. Mif2 contacts one side of the nucleosome dyad, engaging with both Cse4 residues and AT-rich nucleosomal DNA. Both interactions are directed by a contiguous DNA- and histone-binding domain (DHBD) harboring the conserved CENP-C motif, an AT hook, and RK clusters (clusters enriched for arginine–lysine residues). Human CENP-C has two related DHBDs that bind preferentially to DNA sequences of higher AT content. Our findings suggest that a DNA composition-based mechanism together with residues characteristic for the CENP-A histone variant contribute to the specification of centromere identity.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.304782.117.
- Received July 13, 2017.
- Accepted October 5, 2017.
This is a work of the US Government.
