Strongin Daniel E, Groudine Mark, Politz Joan C Ritland
a Division of Basic Sciences; Fred Hutchinson Cancer Research Center; Seattle, WA USA.
Nucleus. 2014 Sep-Oct;5(5):474-81. doi: 10.4161/nucl.36233.
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.
位于不同染色体上的基因座可优先共定位于细胞核中。然而，介导这种空间接近性的许多机制仍有待阐明。12号染色体上的免疫球蛋白重链（IgH）基因座和15号染色体上的原癌基因Myc基因座是研究较多的小鼠B细胞基因共定位模型，在该模型中，这两个基因座以高于预期的频率紧密相邻。这些基因座也是导致小鼠浆细胞瘤和伯基特淋巴瘤的染色体易位中的伙伴。由于在最常研究的小鼠品系中，12号染色体和15号染色体都携带核仁组织区（NORs），我们推测NOR介导的IgH和Myc基因座与共享核仁的拴系可能是驱动IgH:Myc共定位的一种机制。利用在不同染色体组上天然携带核仁组织区（NORs）的小鼠品系，我们证实IgH和Myc以NOR依赖的方式定位于核仁附近，并表明它们与核仁的联合关联显著增加了IgH和Myc配对的频率。因此，我们证明简单的核仁拴系可以增加携带NOR的染色体上基因的共定位频率。
