Long-Range Directional Movement of an Interphase Chromosome Site

SummaryIncreasing evidence suggests functional compartmentalization of interphase nuclei [1]. This includes preferential interior localization of gene-rich and early replicating chromosome regions versus peripheral localization of gene-poor and late replicating chromosome regions 2 and 3, association of some active genes with nuclear speckles 4 and 5 or transcription “factories” [6], and association of transcriptionally repressed genes with heterochromatic regions [7]. Dynamic changes in chromosome compartmentalization 7, 8 and 9 imply mechanisms for long-range interphase chromatin movements. However, live cell imaging in mammalian cells has revealed limited chromatin mobility [10], described as “constrained diffusion” [11]. None of these studies, though, have examined a chromosome locus undergoing an inducible repositioning between two different nuclear compartments. Here we demonstrate migration of an interphase chromosome site from the nuclear periphery to the interior 1–2 hr after targeting a transcriptional activator to this site. Spot redistribution is perturbed by specific actin or nuclear myosin I mutants. Extended periods of chromosome immobility are interspersed with several minute periods in which chromosomes move unidirectionally along curvilinear paths oriented roughly perpendicular to the nuclear envelope at velocities of 0.1–0.9 μm/min over distances of 1–5 μm. Our results suggest an active mechanism for fast and directed long-range interphase chromosome movements dependent directly or indirectly on actin/myosin.