Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

By investigating the positioning of all human chromosomes in primary fibroblasts that have left the proliferative cell cycle, we have demonstrated that in cells made quiescent by reversible growth arrest, chromosome positioning is altered considerably. We found that with the removal of serum from the culture medium, chromosome repositioning took less than 15 minutes, required energy and was inhibited by drugs affecting the polymerization of myosin and actin. We also observed that when cells became quiescent, the nuclear distribution of nuclear myosin 1β was dramatically different from that in proliferating cells. If we suppressed the expression of nuclear myosin 1β by using RNA-interference procedures, the movement of chromosomes after 15 minutes in low serum was inhibited. When high serum was restored to the serum-starved cultures, chromosome repositioning was evident only after 24 to 36 hours, and this coincided with a return to a proliferating distribution of nuclear myosin 1β.These findings demonstrate that genome organization in interphase nuclei is altered considerably when cells leave the proliferative cell cycle and that repositioning of chromosomes relies on efficient functioning of an active nuclear motor complex that contains nuclear myosin 1β.Within interphase nuclei, individual chromosomes are organized within their own nuclear space, known as chromosome territories [1,2]. These interphase chromosome territories are organized in a nonrandom manner in the nuclei of human cells and cells from other species [3]. Chromosomes in different species are positioned radially, according to either their gene density [4-9] or their size [10-12] or both [11,13-16]. The nuclear microenvironment within which a chromosome is located could affect its gene regulation, and it has been proposed that whole chromosomes or regions of chromosomes are shifted around the nucleus to control gene expression [17,18]. Active genes appear to come together in a common nuclear space, po