The kinetochore not only ensures accurate chromosome segregation during cell division but also acts as an important signalling platform for various cellular pathways. Kinetochore assembly is thought to be initiated at chromatin containing the specialised histone H3 CENP-A; however, it is unclear how exactly this epigenetic mark mediates formation and maintenance of centromere chromatin. In this study (p. ), Hiroshi Masumoto and co-workers make use of their previously developed human artificial chromosomes, whose centromeres contain a synthetic alpha-satellite DNA array that allows them to tether kinetochore factors and chromatin modifiers, to address the role of CENP-A in de novo kinetochore formation. They find that many structural kinetochore factors can induce CENP-A deposition and kinetochore formation when the array is at an ectopic site (i.e. not a centromere). The authors demonstrate that these factors recruit CENP-C, which then recruits Mis18-binding protein 1 (M18BP1), a crucial factor for CENP-A deposition. Interestingly, M18BP1 on its own is unable to mediate de novo CENP-A deposition. Furthermore, CENP-I was found to reinforce CENP-A assembly at the centromere by also being able to recruit M18BP1; this occurs in parallel with its recruitment by CENP-C. On the basis of these results, the authors suggest that CENP-C and CENP-I are key factors that coordinate two important mechanisms required for accurate chromosome segregation, kinetochore assembly and epigenetic centromere maintenance.
