Adlam M, Duncan D D, Ng D K, Siu G
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Int Immunol. 1997 Jun;9(6):877-87. doi: 10.1093/intimm/9.6.877.
Developmental expression of the CD4 gene in mature T cells is controlled by at least four transcriptional control elements: a promoter, two enhancers and a silencer. In this report we use a transgenic approach to study the mechanisms in which these elements interact to convey appropriate tissue- and cell-specific expression at all stages of T cell development. Our data indicate that the control of CD4 gene expression requires the interaction of multiple elements functioning in different combinations at different stages of T cell development. Expression of the CD4 gene in immature CD4+CD8+ thymocytes requires a third enhancer element located in the 3' flanking region of the CD4 gene. Interestingly, the CD4 promoter and proximal/distal enhancers first begin to function at the HSAlo CD69lo H-2Khi CD4 single-positive stage; cells of this phenotype are believed to have survived positive selection. These data indicate that the CD4 promoter and late enhancer elements are induced by positive selection; thus, the final maturation process is an active event that requires the initiation of a novel program of gene expression.
成熟T细胞中CD4基因的发育表达受至少四个转录控制元件调控：一个启动子、两个增强子和一个沉默子。在本报告中，我们采用转基因方法研究这些元件相互作用的机制，以便在T细胞发育的各个阶段传递适当的组织和细胞特异性表达。我们的数据表明，CD4基因表达的调控需要多个元件在T细胞发育的不同阶段以不同组合发挥作用。CD4基因在未成熟的CD4+CD8+胸腺细胞中的表达需要位于CD4基因3'侧翼区域的第三个增强子元件。有趣的是，CD4启动子和近端/远端增强子首先在HSAlo CD69lo H-2Khi CD4单阳性阶段开始发挥作用；具有这种表型的细胞被认为已经通过了阳性选择。这些数据表明，CD4启动子和晚期增强子元件是由阳性选择诱导的；因此，最终的成熟过程是一个活跃的事件，需要启动一个新的基因表达程序。
