A CRISPR view of the genome in living cells: Cell cycle and genomic distance dependent dynamics of chromosomal loci

Abstract

In contrast to the well-studied condensation and folding of chromosomes during mitosis, their dynamics during interphase are less understood. We deployed our newly developed, brightness-enhanced CRISPR-based DNA imaging system (CRISPR-Sirius, Ma et al., 2018) to track the dynamics of genomic loci situated kilobases to megabases apart on a single chromosome. Two distinct modes of dynamics were resolved: local movements as well as translational movements of the entire domain within the nucleoplasm. The magnitude of both of these modes of movements increased from early to late G1, whereas the translational movements were reduced in early S. The local fluctuations decreased slightly in early S and more markedly in mid-late S. These results (Ma el al. J. Cell Biol., in press) suggest an ongoing compaction-relaxation dynamic of the interphase chromosome fiber, operating concurrently with changes in the extent of overall translational movements of loci in the 4D nucleome. The former possibility was anticipated some time ago (Pederson, 1972) and the latter shortly thereafter (Crick, 1978). It is too soon to know the full meaning of these interphase chromosome dynamics but all the tools to access this dimension of genome biology are fortunately now at hand.