4.4 Article

Proliferation-dependent positioning of individual centromeres in the interphase nucleus of human lymphoblastoid cell lines

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MOLECULAR BIOLOGY OF THE CELL
卷 26, 期 13, 页码 2550-2560

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AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E14-05-1002

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  1. Centre National de la Recherche Scientifique
  2. Institut National de la Sante et de la Recherche Medicale
  3. Convergence Program of the Universite Pierre et Marie Curie

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The cell nucleus is a highly organized structure and plays an important role in gene regulation. Understanding the mechanisms that sustain this organization is therefore essential for understanding genome function. Centromeric regions (CRs) of chromosomes have been known for years to adopt specific nuclear positioning patterns, but the significance of this observation is not yet completely understood. Here, using a combination of fluorescence in situ hybridization and immunochemistry on fixed human cells and high-throughput imaging, we directly and quantitatively investigated the nuclear positioning of specific human CRs. We observe differential attraction of individual CRs toward both the nuclear border and the nucleoli, the former being enhanced in nonproliferating cells and the latter being enhanced in proliferating cells. Similar positioning patterns are observed in two different lymphoblastoid cell lines. Moreover, the positioning of CRs differs from that of noncentromeric regions, and CRs display specific orientations within chromosome territories. These results suggest the existence of not-yet-characterized mechanisms that drive the nuclear positioning of CRs and therefore pave the way toward a better understanding of how CRs affect nuclear organization.

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