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Nucleolar tethering mediates pairing between the IgH and Myc loci

机译：核仁束缚介导IgH和Myc基因座之间的配对

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摘要

Gene loci on different chromosomes can preferentially colocalize in the cell nucleus. However, many of the mechanisms mediating this spatial proximity remain to be elucidated. The IgH locus on Chromosome 12 and the Myc locus on Chromosome 15 are a well-studied model for gene colocalization in murine B cells, where the two loci are positioned in close proximity at a higher than expected frequency. These gene loci are also partners in the chromosomal translocation that causes murine plasmacytoma and Burkitt’s lymphoma. Because both Chromosome 12 and Chromosome 15 carry nucleolar organizer regions (NORs) in the most commonly studied mouse strains, we hypothesized that NOR-mediated tethering of the IgH and Myc loci to shared nucleoli could serve as a mechanism to drive IgH:Myc colocalization. Using mouse strains that naturally carry nucleolar organizer regions (NORs) on different sets of chromosomes, we establish that IgH and Myc are positioned proximal to nucleoli in a NOR dependent manner and show that their joint association with nucleoli significantly increases the frequency of IgH and Myc pairing. Thus we demonstrate that simple nucleolar tethering can increase the colocalization frequency of genes on NOR-bearing chromosomes.
机译：不同染色体上的基因位点可以优先共定位在细胞核中。然而，许多介导这种空间接近性的机制仍有待阐明。染色体12上的IgH基因座和染色体15上的Myc基因座是鼠B细胞中基因共定位的经过充分研究的模型，其中两个基因座以比预期高的频率紧密靠近。这些基因位点也是导致小鼠浆细胞瘤和伯基特淋巴瘤的染色体易位的伙伴。由于12号染色体和15号染色体在最常研究的小鼠品系中均带有核仁组织区（NORs），因此我们假设NOR介导的 IgH和 Myc基因座与共享核仁的系链可以作为一种机制驱动器 IgH：Myc共定位。使用天然在不同染色体组上携带核仁组织区（NORs）的小鼠品系，我们确定 IgH和 Myc以NOR依赖性方式位于核仁附近，并显示它们与核仁的联合显着增加 IgH和 Myc配对的频率。因此，我们证明了简单的核仁束缚可以增加NOR染色体上基因的共定位频率。

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