Laboratoire de Radiobiologie et d'Oncologie (LRO), Commissariat à l'Energie Atomique, 92 265 Fontenay-aux-Roses Cedex, France.
J Cell Sci. 2010 Dec 1;123(Pt 23):4063-75. doi: 10.1242/jcs.066498.
The organization of chromosomes is important for various biological processes and is involved in the formation of rearrangements often observed in cancer. In mammals, chromosomes are organized in territories that are radially positioned in the nucleus. However, it remains unclear whether chromosomes are organized relative to each other. Here, we examine the nuclear arrangement of 10 chromosomes in human epithelial cancer cells by three-dimensional FISH analysis. We show that their radial position correlates with the ratio of their gene density to chromosome size. We also observe that inter-homologue distances are generally larger than inter-heterologue distances. Using numerical simulations taking radial position constraints into account, we demonstrate that, for some chromosomes, radial position is enough to justify the inter-homologue distance, whereas for others additional constraints are involved. Among these constraints, we propose that nucleolar organizer regions participate in the internal positioning of the acrocentric chromosome HSA21, possibly through interactions with nucleoli. Maintaining distance between homologous chromosomes in human cells could participate in regulating genome stability and gene expression, both mechanisms that are key players in tumorigenesis.
染色体的组织对于各种生物过程都很重要，并且参与了癌症中经常观察到的重排的形成。在哺乳动物中，染色体组织成在核中呈放射状定位的区域。然而，目前尚不清楚染色体是否彼此相对组织。在这里，我们通过三维 FISH 分析检查了人类上皮癌细胞中的 10 条染色体的核排列。我们表明，它们的放射状位置与基因密度与染色体大小的比值相关。我们还观察到，同系物之间的距离通常大于非同系物之间的距离。通过考虑放射状位置约束的数值模拟，我们证明，对于某些染色体，放射状位置足以证明同系物之间的距离是合理的，而对于其他染色体则涉及其他约束。在这些约束中，我们提出核仁组织者区域可能通过与核仁的相互作用参与着丝粒染色体 HSA21 的内部定位。在人类细胞中保持同源染色体之间的距离可能有助于调节基因组稳定性和基因表达，这两个机制都是肿瘤发生的关键因素。
