Dynamic genome-wide interaction patterns elucidate the roles of Ki67 in chromatin organization

Ki67 is a widely-used proliferation marker with functions in chromosomal organization. It forms a protective layer around mitotic chromosomes and is involved in genome positioning in interphase. However, a detailed understanding of how Ki67 organizes the genome was still lacking, partially because genome-wide interaction profiles were missing. Here, we generate DNA-Ki67 interaction profiles using our pA-DamID method, and show that Ki67 interacts with the genome in a domain-like pattern that partially overlaps with lamina-associated domains. Overall design: DNA-Ki67 interactions were profiled with pA-DamID in three human cell lines, throughout the cell cycle and following various nucleolar perturbation experiments. Additionally, Ki67 interactions were compared to Lamin B1 interactions and H3K27me3 and H3K9me3 in normal and perturbed conditions. Finally, the functional role of Ki67 was determined by profiling gene expression data (RNA-seq), replication timing (Repli-seq) and genome interactions (Hi-C).