Important roles for E protein binding sites within the immunoglobulin kappa chain intronic enhancer in activating Vkappa Jkappa rearrangement.
Important roles for E protein binding sites within the immunoglobulin kappa chain intronic enhancer in activating Vkappa Jkappa rearrangement.
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DOI：
10.1084/jem.20041135
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发表时间：
2004-11-01
期刊：
影响因子：
--
通讯作者：
Xu Y
中科院分区：
文献类型：
--
作者：
Inlay MA;Tian H;Lin T;Xu Y
免疫球蛋白κ轻链内含子增强子（iEκ）激活κ重排，并且需要维持κ相对于λ（λ）的更早或更有效的重排。为了理解iEκ如何调节κ重排的机制，我们采用同源重组来突变内源性κ基因座中iEκ内的单个功能基序，包括NF-κB结合位点（κB）以及κE1、κE2和κE3 E盒。对这些突变影响的分析显示，κE2和较小程度的κE1（而不是κE3）对激活κ重排很重要。令人惊讶的是，κB位点的突变对κ重排没有明显影响。与整个iEκ的缺失相比，κE1和κE2的同时突变比κE1或κE2单独突变更显著地降低κ重排的效率。由于E2 A家族蛋白是唯一已知的与这些E盒结合的因子，这些发现提供了明确的证据，表明E2 A是κ重排的关键调节因子。
The immunoglobulin κ light chain intronic enhancer (iEκ) activates κ rearrangement and is required to maintain the earlier or more efficient rearrangement of κ versus lambda (λ). To understand the mechanism of how iEκ regulates κ rearrangement, we employed homologous recombination to mutate individual functional motifs within iEκ in the endogenous κ locus, including the NF-κB binding site (κB), as well as κE1, κE2, and κE3 E boxes. Analysis of the impacts of these mutations revealed that κE2 and to a lesser extent κE1, but not κE3, were important for activating κ rearrangement. Surprisingly, mutation of the κB site had no apparent effect on κ rearrangement. Comparable to the deletion of the entire iEκ, simultaneous mutation of κE1 and κE2 reduces the efficiency of κ rearrangement much more dramatically than either κE1 or κE2 mutation alone. Because E2A family proteins are the only known factors that bind to these E boxes, these findings provide unambiguous evidence that E2A is a key regulator of κ rearrangement.
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