Henderson A J, McDougall S, Leiden J, Calame K L
Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Mol Cell Biol. 1994 Jun;14(6):4286-94. doi: 10.1128/mcb.14.6.4286-4294.1994.
Three high-affinity binding sites for the GATA family of transcriptional regulators have been identified within the T-cell receptor beta-chain (TCR beta) transcriptional enhancer, and their functional significance has been determined in an effort to understand the T-cell specificity of the enhancer more fully. One site, TE4, is important for activity of the enhancer in T cells. Neither site TE1 nor site TE2 can functionally replace a mutated TE4 site in T cells; however, the same protein, probably GATA-3, binds all three sites, as judged by electrophoretic mobility shift, oligonucleotide competition, and proteolytic clipping assays. These data suggest that additional proteins are critical for the ability of GATA-3 to activate the TCR beta enhancer. In fibroblasts, the GATA sequence at site TE1 appears to bind a negative regulator. Since this is not true in B cells, B cells and fibroblasts appear to have different mechanisms for negative regulation of the TCR beta enhancer.
在T细胞受体β链(TCRβ)转录增强子内已鉴定出转录调节因子GATA家族的三个高亲和力结合位点,并确定了它们的功能意义,以便更全面地了解该增强子的T细胞特异性。一个位点TE4对增强子在T细胞中的活性很重要。在T细胞中,位点TE1和位点TE2都不能在功能上替代突变的TE4位点;然而,通过电泳迁移率变动分析、寡核苷酸竞争分析和蛋白水解切割分析判断,同一种蛋白(可能是GATA-3)与所有这三个位点结合。这些数据表明,其他蛋白对于GATA-3激活TCRβ增强子的能力至关重要。在成纤维细胞中,位点TE1处的GATA序列似乎结合一种负调节因子。由于在B细胞中并非如此,B细胞和成纤维细胞似乎具有不同的TCRβ增强子负调节机制。