Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts.
BACKGROUND
Radial chromosome positioning in interphase nuclei is nonrandom and can alter according to developmental, differentiation, proliferation, or disease status. However, it is not yet clear when and how chromosome repositioning is elicited.


RESULTS
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 1 beta was dramatically different from that in proliferating cells. If we suppressed the expression of nuclear myosin 1 beta 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 1 beta.


CONCLUSIONS
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 1 beta.
Mehta
Ishita S
IS
Centre for Cell and Chromosome Biology, Division of Biosciences, School of Health Sciences and Social Care, Brunel University, Kingston Lane, Uxbridge, UB8 3PH, UK. ishita.mehta@brunel.ac.uk
Amira
Manelle
M
Harvey
Amanda J
AJ
Bridger
Joanna M
JM
D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D002875:Chromosomes / Q000378:metabolism / Q000648:ultrastructure*; D005347:Fibroblasts / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008954:Models, Biological; D009218:Myosins / Q000378:metabolism; D034622:RNA Interference; D024723:Ventricular Myosins / Q000378:metabolism
D000199:Actins; D000251:Adenosine Triphosphatases; D020558:GTP Phosphohydrolases; D024723:Ventricular Myosins; D009218:Myosins