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首页> 外文期刊>Molecular and Cellular Biology >A New Element within the T-Cell Receptor α Locus Required for Tissue-Specific Locus Control Region Activity
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A New Element within the T-Cell Receptor α Locus Required for Tissue-Specific Locus Control Region Activity

机译：组织特定基因座控制区活动所需的T细胞受体α基因座中的新元素

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Locus control regions (LCRs) are cis-acting regulatory elements thought to provide a tissue-specific open chromatin domain for genes to which they are linked. The gene for T-cell receptor α chain (TCRα) is exclusively expressed in T cells, and the chromatin at its locus displays differentially open configurations in expressing and nonexpressing tissues. Mouse TCRα exists in a complex locus containing three differentially regulated genes. We previously described an LCR in this locus that confers T-lineage-specific expression upon linked transgenes. The 3′ portion of this LCR contains an unrestricted chromatin opening activity while the 5′ portion contains elements restricting this activity to T cells. This tissue-specificity region contains four known DNase I hypersensitive sites, two located near transcriptional silencers, one at the TCRα enhancer, and another located 3′ of the enhancer in a 1-kb region of unknown function. Analysis of this region using transgenic mice reveals that the silencer regions contribute negligibly to LCR activity. While the enhancer is required for complete LCR function, its removal has surprisingly little effect on chromatin structure or expression outside the thymus. Rather, the region 3′ of the enhancer appears responsible for the tissue-differential chromatin configurations observed at the TCRα locus. This region, herein termed the “HS1′ element,” also increases lymphoid transgene expression while suppressing ectopic transgene activity. Thus, this previously undescribed element is an integral part of the TCRαLCR, which influences tissue-specific chromatin structure and gene expression.
机译：基因座控制区（LCRs）是顺式作用的调控元件，被认为为与其相连的基因提供了组织特异性的染色质结构域。 T细胞受体α链（TCRα）的基因仅在T细胞中表达，其染色质在表达和非表达组织中均显示差异开放的构型。小鼠TCRα存在于一个复杂的基因座中，该基因座包含三个差异调节基因。我们先前在该基因座中描述了一个LCR，该LCR在链接的转基因上赋予T谱系特异性表达。该LCR的3'部分包含不受限制的染色质开放活性，而5'部分包含将这种活性限制于T细胞的元素。该组织特异性区域包含四个已知的DNase I超敏位点，两个位于转录沉默子附近，一个位于TCRα增强子，另一个位于增强子的3'处，未知功能的1kb区域。使用转基因小鼠对该区域的分析表明，沉默子区域对LCR活性的贡献可忽略不计。虽然增强子是完整LCR功能所必需的，但令人惊讶的是，去除它对染色质结构或在胸腺外的表达几乎没有影响。而是，增强子的区域3'似乎负责TCRα基因座处观察到的组织差异染色质构型。在本文中称为“ HS1'元件”的该区域还增加了淋巴样转基因表达，同时抑制了异位转基因活性。因此，该先前未描述的元素是TCRαLCR的组成部分，它影响组织特异性染色质结构和基因表达。

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