Global chromosome positions are transmitted through mitosis in mammalian cells.
We investigated positioning of chromosomes during the cell cycle in live mammalian cells with a combined experimental and computational approach. By non-invasive labeling of chromosome subsets and tracking by 4D imaging, we could show that no global rearrangements occurred in interphase. Using the same assay, we also observed a striking order of chromosomes throughout mitosis. By contrast, our computer simulation based on stochastic movements of individual chromosomes predicted randomization of chromosome order in mitosis. In vivo, a quantitative assay for single chromosome positioning during mitosis revealed strong similarities between daughter and mother cells. These results demonstrate that global chromosome positions are heritable through the cell cycle in mammalian cells. Based on tracking of labeled chromosomes and centromeres during chromosome segregation and experimental perturbations of chromosomal order, we propose that chromosome specific timing of sister chromatid separation transmits chromosomal positions from one cell generation to the next.
Gerlich
Daniel
D
Intelligent Bioinformatics Systems, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.
Beaudouin
Joël
J
Kalbfuss
Bernd
B
Daigle
Nathalie
N
Eils
Roland
R
Ellenberg
Jan
J
D000818:Animals; D006690:Bisbenzimidazole / Q000494:pharmacology; D002467:Cell Nucleus / Q000648:ultrastructure; D002478:Cells, Cultured; D002503:Centromere / Q000648:ultrastructure; D002875:Chromosomes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D003198:Computer Simulation; D049452:Green Fluorescent Proteins; D006657:Histones / Q000378:metabolism; D007399:Interphase; D007668:Kidney; D008164:Luminescent Proteins / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D051381:Rats; D012680:Sensitivity and Specificity; D008941:Spindle Apparatus / Q000502:physiology
D006657:Histones; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D006690:Bisbenzimidazole