Long-Range Directional Movement of an Interphase Chromosome Site

Increasing 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, 3], association of some active genes with nuclear speckles [4, 5] or transcription "factories" [6], and association of transcriptionally repressed genes with heterochromatic regions [7]. Dynamic changes in chromosome compartmentalization [7-9] 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.