A conserved transcriptional enhancer regulates RAG gene expression in developing B cells
A conserved transcriptional enhancer regulates RAG gene expression in developing B cells
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DOI：
10.1016/s1074-7613(03)00181-x
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发表时间：
2003-07-01
期刊：
影响因子：
32.4
通讯作者：
Schlissel, MS
中科院分区：
文献类型：
--
作者：
Hsu, LY;Lauring, J;Schlissel, MS
虽然RAG1和RAG2基因的表达是淋巴细胞发育所必需的，但对这些基因的淋巴特异性和发育阶段特异性调控的机制知之甚少。我们已经确定了一种新的，进化上保守的转录增强子在RAG基因座，称为Erag，这是必不可少的染色体报告基因的表达驱动的RAG启动子。小鼠生殖系中Erag的靶向缺失导致与缺陷型V（D）J重组相关的B细胞发育的部分阻断，而T细胞发育似乎不受影响。我们发现，E2A转录因子结合到Erag在体内，并可以反式激活Erag依赖的报告结构在共转染的细胞系。这些发现使我们得出结论，RAG转录是由不同的元素在发展B和T细胞和Erag是必需的RAG表达的最佳水平在早期B细胞前体，但不是在T细胞。
Although expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood. We have identified a novel, evolutionarily conserved transcriptional enhancer in the RAG locus, called Erag, which was essential for the expression of a chromosomal reporter gene driven by either RAG promoter. Targeted deletion of Erag in the mouse germline results in a partial block in B cell development associated with deficient V(D)J recombination, whereas T cell development appears unaffected. We found that E2A transcription factors bind to Erag in vivo and can transactivate Erag-dependent reporter constructs in cotransfected cell lines. These findings lead us to conclude that RAG transcription is regulated by distinct elements in developing B and T cells and that Erag is required for optimal levels of RAG expression in early B cell precursors but not in T cells.