The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor.
The T alpha 2 nuclear protein binding site from the human T cell receptor alpha enhancer functions as both a T cell-specific transcriptional activator and repressor.
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人类 T 细胞受体 α 增强子的 T α2 核蛋白结合位点既充当 T 细胞特异性转录激活子又充当阻遏子。
DOI：
10.1084/jem.172.5.1443
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Leiden,JM
中科院分区：
文献类型：
--
作者：
Ho,IC;Leiden,JM
人类T细胞受体α (tcr - α)基因的T细胞特异性表达是由可变区启动子元件与位于tcr - α恒定区（C α）基因片段4.5 kb 3'的转录增强子相互作用调控的。最小的tcr - α增强子由两个核蛋白结合位点T α 1和T α 2组成，这两个位点都是增强子T细胞特异性活性所必需的。T α 1结合位点包含一个共识cAMP反应元件（CRE），并结合一组普遍存在的核蛋白。T α 2结合位点不包含已知的转录增强子基序。然而，它结合至少两种核蛋白复合物，其中一种是T细胞特异性的。我们现在报道，尽管T α 2核蛋白结合位点在tcr - α增强子的背景下显示转录激活子活性，但当定位在几个异源启动子和增强子元件的上游或下游时，该位点单独可以作为一个有效的T细胞特异性转录抑制因子发挥作用。这些结果表明，单个核蛋白结合位点可以作为T细胞特异性转录激活因子或抑制因子，这取决于它所处的环境。
T cell-specific expression of the human T cell receptor alpha (TCR-alpha) gene is regulated by the interaction of variable region promoter elements with a transcriptional enhancer that is located 4.5 kb 3' of the TCR-alpha constant region (C alpha) gene segment. The minimal TCR-alpha enhancer is composed of two nuclear protein binding sites, T alpha 1 and T alpha 2, that are both required for the T cell-specific activity of the enhancer. The T alpha 1 binding site contains a consensus cAMP response element (CRE), and binds a set of ubiquitous nuclear proteins. The T alpha 2 binding site does not contain known transcriptional enhancer motifs. However, it binds at least two nuclear protein complexes, one of which is T cell specific. We now report that although the T alpha 2 nuclear protein binding site displays transcriptional activator activity in the context of the TCR-alpha enhancer, this site alone can function as a potent, T cell-specific transcriptional repressor when positioned either upstream, or downstream of several heterologous promoter and enhancer elements. These results demonstrate that a single nuclear protein binding site can function as a T cell-specific transcriptional activator or repressor element, depending upon the context in which it is located.