Summary
Histone variants fine-tune transcription, replication, DNA damage repair, and faithful chromosome segregation. The histone H3 variant CENP-A/CENH3 seeds the kinetochore, creating the physical interface between centromeric chromatin and mitotic spindles. How kinetochore proteins modify CENP-A nucleosome dynamics and how these dynamics affect centromere chromatin is poorly understood. Using interdisciplinary analyses, we report that CENP-A nucleosomes are intrinsically more elastic than H3 nucleosomes, and that the kinetochore component CENP-C suppresses this innate elasticity. Shifting the balance between elastic and stiffer CENP-A states in vivo results in the suppression of centromeric chromatin plasticity, so that centromeric chromatin becomes less permissive to RNA polymerase 2, thereby diminishing new CENP-A loading, ensuing in mitotic defects. Restoring this balance rescues mitotic defects. Together, these data provide a link between innate structural properties possessed by histone variant nucleosomes, the adaptability of chromatin states in vivo, and the epigenetic plasticity of the underlying locus.