Association between the Igk and Igh immunoglobulin loci mediated by the 3′ Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells
Association between the Igk and Igh immunoglobulin loci mediated by the 3′ Igk enhancer induces 'decontraction' of the Igh locus in pre-B cells
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DOI：
10.1038/ni1567
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发表时间：
2008-04-01
影响因子：
30.5
通讯作者：
Skok, Jane A.
中科院分区：
文献类型：
--
作者：
Hewitt, Susannah L.;Farmer, Deborah;Skok, Jane A.
在编码免疫球蛋白重链（Igh）和免疫球蛋白轻链（Igk）的基因座处的可变（多样性）连接（V（D）J）重组在B细胞发育的连续阶段期间顺序地发生。使用三维DNA荧光原位杂交，在这里，我们确定了这两个位点，标志着IgH和IgK重组之间的过渡的谱系特异性和阶段特异性染色体间的关联。共定位发生在前B细胞中位于着丝粒周围的等位基因之间，并由3' Igk增强子介导。这种调控元件的删除防止关联的Igh和Igk基因座，抑制pericentromeric招聘和位点的Igh等位基因的“decentraction”，并导致更大的远端重排的基因编码的可变重链区。我们的数据表明Igk基因座及其3'增强子参与了将Igh基因座引导至抑制性核亚室并诱导Igh基因座去收缩。
Variable-(diversity)-joining (V(D)J) recombination at loci encoding the immunoglobulin heavy chain (Igh) and immunoglobulin light chain (Igk) takes place sequentially during successive stages in B cell development. Using three-dimensional DNA fluorescence in situ hybridization, here we identify a lineage-specific and stage-specific interchromosomal association between these two loci that marks the transition between Igh and Igk recombination. Colocalization occurred between pericentromerically located alleles in pre-B cells and was mediated by the 3' Igk enhancer. Deletion of this regulatory element prevented association of the Igh and Igk loci, inhibited pericentromeric recruitment and locus 'decontraction' of an Igh allele, and resulted in greater distal rearrangement of the gene encoding the variable heavy-chain region. Our data indicate involvement of the Igk locus and its 3' enhancer in directing the Igh locus to a repressive nuclear subcompartment and inducing the Igh locus to decontract.