Redundant and unique roles of two enhancer elements in the TCRγ locus in gene regulation and γδ T cell development
Redundant and unique roles of two enhancer elements in the TCRγ locus in gene regulation and γδ T cell development
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DOI：
10.1016/s1074-7613(02)00285-6
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发表时间：
2002-03-01
期刊：
影响因子：
32.4
通讯作者：
Raulet, DH
中科院分区：
文献类型：
--
作者：
Xiong, N;Kang, CH;Raulet, DH
许多哺乳动物基因，包括那些编码抗原受体的基因，含有一个以上的增强子元件。删除一个元件通常不会阻止表达，但功能冗余从未通过多个元件的基因靶向直接证明。我们证明，同时删除两个增强子/LCR样元件在TCR C γ 1簇，HsA和3 'E-C γ 1，严重减少TCR γ转录，选择性损害发展的γ δ胸腺细胞亚群，但只有适度减少TCR γ基因重排，而删除每个元素分别有很小的影响。与胸腺细胞中的这些结果相反，单独缺失HsA降低了外周γ δ T细胞中特异性的一个V γ基因的转录。因此，这两个元件在胸腺细胞中表现出功能冗余，但在其他环境中也具有独特的功能。
Many mammalian genes, including those encoding antigen receptors, contain more than one enhancer element. Deleting one element often does not prevent expression, but functional redundancy has never been directly demonstrated by gene targeting of multiple elements. We demonstrate that simultaneous deletion of two enhancer/LCR-like elements in the TCR Cgamma1 cluster, HsA and 3'E-Cgamma1, severely diminishes TCRgamma transcription, selectively impairs development of gammadelta thymocyte subsets, but only modestly reduces TCRgamma gene rearrangement, while deletion of each element separately has little effect. In contrast to these results in thymocytes, deletion of HsA alone reduces transcription of one Vgamma gene specifically in peripheral gammadelta T cells. Thus, the two elements exhibit functional redundancy in thymocytes but also have unique functions in other settings.