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首页> 外文期刊>Molecular and Cellular Biology >Sites That Direct Nuclear Compartmentalization Are near the 5′ End of the Mouse Immunoglobulin Heavy-Chain Locus
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Sites That Direct Nuclear Compartmentalization Are near the 5′ End of the Mouse Immunoglobulin Heavy-Chain Locus

机译：直接核分隔的位点在小鼠免疫球蛋白重链基因座的5'端附近

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VDJ rearrangement in the mouse immunoglobulin heavy chain (Igh) locus involves a combination of events, including a large change in its nuclear compartmentalization. Prior to rearrangement, Igh moves from its default peripheral location near the nuclear envelope to an interior compartment, and after rearrangement it returns to the periphery. To identify any sites in Igh responsible for its association with the periphery, we systematically analyzed the nuclear positions of the Igh locus in mouse non-B- and B-cell lines and, importantly, in primary splenic lipopolysaccharide-stimulated B cells and plasmablasts. We found that a broad ～1-Mb region in the 5′ half of the variable-gene region heavy-chain (Vh) locus regularly colocalizes with the nuclear lamina. The 3′ half of the Vh gene region is less frequently colocalized with the periphery, while sequences flanking the Vh gene region are infrequently so. Importantly, in plasmacytomas, VDJ rearrangements that delete most of the Vh locus, including part of the 5′ half of the Vh gene region, result in loss of peripheral compartmentalization, while deletion of only the proximal half of the Vh gene region does not. In addition, when Igh-Myc translocations move the Vh genes to a new chromosome, the distal Vh gene region is still associated with the nuclear periphery. Thus, the Igh region that interacts with the nuclear periphery is localized but is likely comprised of multiple sites that are distributed over ～1 Mb in the 5′ half of the Vh gene region. This 5′ Vh gene region that produces peripheral compartmentalization is the same region that is distinguished by requirements for interleukin-7, Pax5, and Ezh2 for rearrangement of the Vh genes.
机译：小鼠免疫球蛋白重链（Igh）基因座中的VDJ重排涉及多种事件的组合，包括其核区室化的较大变化。在重新布置之前，Igh从其默认的外围位置（靠近核外壳）移动到内部隔室，并在重新布置之后返回周围。为了确定Igh中与其外围关联的任何位点，我们系统地分析了Igh基因座在小鼠非B细胞和B细胞系，以及重要的是在脾脏脂多糖刺激的B细胞和成浆细胞中的核位置。我们发现，在可变基因区重链（Vh）基因座的5'一半中，宽广的〜1-Mb区与核层通常共定位。 Vh基因区的3'半部分很少与外围共定位，而位于Vh基因区侧翼的序列则很少。重要的是，在浆细胞瘤中，删除大部分Vh基因座（包括Vh基因区域5'一半的一部分）的VDJ重排会导致外围区室化的丧失，而仅删除Vh基因区域的近端部分却不会。此外，当Igh-Myc易位将Vh基因移​​动到新染色体时，远侧Vh基因区域仍与核外围相关。因此，与核外围相互作用的Igh区是局部的，但可能由多个位点组成，这些位点分布在Vh基因区的5'一半〜1 Mb上。产生外周区室化的5'Vh基因区域是同一区域，该区域的区别在于对Vh基因的重排需要白介素7，Pax5和Ezh2。

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