A LOCUS-CONTROL REGION IN THE T-CELL RECEPTOR ALPHA/DELTA LOCUS
A LOCUS-CONTROL REGION IN THE T-CELL RECEPTOR ALPHA/DELTA LOCUS
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DOI：
10.1016/1074-7613(94)90099-x
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发表时间：
1994-06-01
期刊：
影响因子：
32.4
通讯作者：
WINOTO, A
中科院分区：
文献类型：
--
作者：
DIAZ, P;CADO, D;WINOTO, A
基因座控制区（LCR）是一组调节基因座染色质可及性的顺式作用元件。在T细胞受体(TCR) α / δ位点，LCR可能调控TCR α和δ基因的组织和发育差异表达以及重排。我们定位了TCR α / δ位点的3'区，其中包含8个T细胞特异性核酸酶超敏感结构域（HS-1至HS-8），符合LCR的特征。在转基因小鼠中，与该区域相关的TCR α基因在高水平表达，与整合位点无关，并与基因拷贝数相关。转基因在α - β T细胞亚群中表达，而不是在γ - δ T细胞亚群中表达，并在发育过程中的适当时间被激活。正常的LCR功能需要包含HS-2到HS-6的区域。我们提出了一个LCR竞争模型来解释TCR α和δ基因在发育过程中的差异调控。
A locus control region (LCR) is a set of cis-acting elements that regulate chromatin accessibility of a gene locus. In the T cell receptor (TCR) alpha/delta locus, an LCR might regulate the differential tissue and developmental expression and the rearrangement of TCR alpha and delta genes. We have localized a region 3' of the TCR alpha/delta locus containing eight T cell-specific nuclease hypersensitive domains (HS-1 to HS-8), which fit the characteristics of an LCR. In transgenic mice, a TCR alpha gene linked to this region is expressed at a high level, independent of the site of integration and correlates with gene copy number. The transgene is expressed in the alpha beta but not the gamma delta T cell subset and is activated at the right time during development. Proper LCR function requires the region containing HS-2 to HS-6. We propose a model of LCR competition to explain the differential regulation of TCR alpha versus delta genes during development.