FBS Colloquia No.366Laboratory of Chromosome Biology

Molecular mechanism for stable inheritance of centromeric chromatin

Accurate chromosome segregation is ensured by the stable maintenance of kinetochores formed at centromeres. In vertebrates, the location of kinetochore formation is specified by a sequence-independent epigenetic mechanism using the CENP-A nucleosome as an epigenetic marker. However, the details of this mechanism remain unclear. The current model proposes that in the G1 phase, the CENP-A-HJURP chaperone complex recognizes the Mis18 complex located on centromeres, leading to CENP-A incorporation into centromeric chromatin. This process allows the maintenance of centromeric chromatin over generations. However, recent analysis using chicken DT40 cells revealed that CENP-A incorporation is not entirely lost even after Mis18 complex knockout, suggesting the existence of an alternative CENP-A incorporation pathway. In this study, we focused on a group of factors capable of de novo induction of centromeres, identified through ectopic localization experiments in DT40 cells, and conducted genetic analyses. We introduce an additional pathway for CENP-A incorporation, including functional analyses based on molecular models obtained from structural predictions.