CRISPR imaging reveals chromatin fluctuation at the centromere region related to cellular senescence

Abstract The human genome is spatially and temporally organized in the nucleus as chromatin, and the dynamic structure of chromatin is closely related to genome functions. Cellular senescence characterized by an irreversible arrest of proliferation is accompanied by chromatin reorganisation in the nucleus during senescence. However, chromatin dynamics in chromatin reorganisation is poorly understood. Here, we report chromatin dynamics at the centromere region during senescence in cultured human cell lines using live imaging based on the clustered regularly interspaced short palindromic repeat/dCas9 system. The repetitive sequence at the centromere region, alpha-satellite DNA, was predominantly detected on chromosomes 1, 12, and 19. Centromeric chromatin formed irregular-shaped domains with high fluctuation in cells undergoing 5′-aza-2′-deoxycytidine-induced senescence. Our findings suggest that the increased fluctuation of the chromatin structure facilitates centromere disorganisation during cellular senescence