Chromosomes. CENP-C reshapes and stabilizes CENP-A nucleosomes at the centromere

• Autor(a) principal: Falk, S. J.
• Data de Publicação: 2015
• Outros Autores: 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., Black, B. E.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.7/627
• topic: Autoantigens; Centromere; Chromosomal Proteins, Non-Histone; DNA; Epigenesis, Genetic; Fluorescence Resonance Energy Transfer; Gene Knockdown Techniques; Humans; Nucleosomes; Protein Structure, Secondary

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.