Hostert A, Tolaini M, Roderick K, Harker N, Norton T, Kioussis D
Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, London, England.
Immunity. 1997 Oct;7(4):525-36. doi: 10.1016/s1074-7613(00)80374-x.
The coreceptors CD4 and CD8 play a crucial role during thymocyte development and T cell effector function, and their expression is developmentally regulated. To determine the underlying molecular mechanisms of CD8 gene regulation we cloned the murine CD8 gene locus from genomic libraries and analyzed this region for deoxyribonuclease (DNase I) hypersensitive sites (HSS). Here we report, using transgenic mice, deletion analysis of one of the identified clusters of DNase I hypersensitivity, consisting of three DNase I-HSS and located in the intergenic region between the CD8alpha and CD8beta genes. Our data show that at least two of the DNase I-HSS constituting this cluster are individually sufficient to direct CD8alpha or heterologous transgene expression to the mature CD8 single-positive T cell subset and that this expression coincides temporally with the appearance of positively selected T cells.
共受体CD4和CD8在胸腺细胞发育和T细胞效应功能中发挥关键作用,并且它们的表达受到发育调控。为了确定CD8基因调控的潜在分子机制,我们从基因组文库中克隆了小鼠CD8基因座,并分析了该区域的脱氧核糖核酸酶(DNase I)超敏位点(HSS)。在此,我们报告利用转基因小鼠对其中一个已鉴定的DNase I超敏簇进行缺失分析,该超敏簇由三个DNase I-HSS组成,位于CD8α和CD8β基因之间的基因间隔区。我们的数据表明,构成该簇的至少两个DNase I-HSS各自足以将CD8α或异源转基因表达导向成熟的CD8单阳性T细胞亚群,并且这种表达在时间上与阳性选择的T细胞的出现相吻合。