Variation in the CENP-A sequence association landscape across diverse inbred mouse strains. Cell Rep. 2023; 42(10):113178
This work was funded by a Maximizing Investigators’ Research Award from the National Institute of General Medical Sciences to B.L.D. (R35 GM133415). U.P.A. was supported by a Ruth L. Kirschtein Predoctoral Individual Fellow- ship from the National Cancer Institute (F31CA268727). CENP-A antibody pro- duction and affinity purification was supported through NIH grants R01 GM124041 and R01 GM129263 awarded to B.A.S. The content of this manu- script is the sole responsibility of the authors and does not necessarily repre- sent the official views of the National Institutes of Health
Centromeres are crucial for chromosome segregation, but their underlying sequences evolve rapidly, imposing strong selection for compensatory changes in centromere-associated kinetochore proteins to assure the stability of genome transmission. While this co-evolution is well documented between species, it remains unknown whether population-level centromere diversity leads to functional differences in kinetochore protein association. Mice (Mus musculus) exhibit remarkable variation in centromere size and sequence, but the amino acid sequence of the kinetochore protein CENP-A is conserved. Here, we apply k-mer-based analyses to CENP-A chromatin profiling data from diverse inbred mouse strains to investigate the interplay between centromere variation and kinetochore protein sequence association. We show that centromere sequence diversity is associated with strain-level differences in both CENP-A positioning and sequence preference along the mouse core centromere satellite. Our findings reveal intraspecies sequence-dependent differences in CENP-A/centromere association and open additional perspectives for understanding centromere-mediated variation in genome stability.