Sarafova S, Siu G
Department of Microbiology and the Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, College of Physicians and Surgeons, 701 West 168th Street, New York, NY 10032, USA.
Nucleic Acids Res. 2000 Jul 15;28(14):2664-71. doi: 10.1093/nar/28.14.2664.
The control of CD4 expression is linked to the signaling events that mediate T-cell development and is directly dependent on the CD4 promoter. The CD4 promoter does not contain functionally redundant sites: all four factor-binding sites must be intact to achieve wild-type activity. Here we demonstrate that the precise position of three factor-binding sites relative to each other is essential for promoter activity, indicating that they function together as an inseparable cassette for assembly of the transcription initiation complex. Small changes in either phasing or distance between any two sites in this cassette leads to complete abrogation of promoter function. In addition, we demonstrate that one of the factors that bind the promoter cassette is not present in CD8 SP T(C) cells. Thus, this factor is a candidate for mediating the relative subclass specificity of CD4 promoter function in activated CD4 SP T(H) cells.
CD4表达的调控与介导T细胞发育的信号转导事件相关联,并且直接依赖于CD4启动子。CD4启动子不包含功能冗余位点:所有四个因子结合位点都必须完整才能实现野生型活性。在此我们证明,三个因子结合位点相对于彼此的精确位置对于启动子活性至关重要,这表明它们作为转录起始复合物组装的不可分割的盒式结构共同发挥作用。该盒式结构中任意两个位点之间的相位或距离的微小变化都会导致启动子功能完全丧失。此外,我们证明结合启动子盒式结构的因子之一在CD8 SP T(C)细胞中不存在。因此,该因子是介导活化的CD4 SP T(H)细胞中CD4启动子功能相对亚类特异性的候选因子。