1. Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere
- Author
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Falk, S. J., Guo, L. Y., Sekulic, N., Smoak, E. M., Mani, T., Logsdon, G. A., Gupta, K., Jansen, L. E. T., Van Duyne, G. D., Vinogradov, S. A., Lampson, M. A., and Black, B. E.
- Subjects
Chromosomal Proteins, Non-Histone ,Gene Knockdown Techniques ,education ,Centromere ,Fluorescence Resonance Energy Transfer ,Humans ,macromolecular substances ,DNA ,Autoantigens ,Protein Structure, Secondary ,Epigenesis, Genetic ,Nucleosomes - Abstract
Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity. NIH grants: (GM082989, CA186430, GM008275, GM008216, GM007229); American Heart Association predoctoral fellowship; American Cancer Society postdoctoral fellowship; NSF grant: (agreement DMR-0944772).
- Published
- 2015