Siu G, Wurster A L, Duncan D D, Soliman T M, Hedrick S M
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032.
EMBO J. 1994 Aug 1;13(15):3570-9. doi: 10.1002/j.1460-2075.1994.tb06664.x.
The appropriate expression of the CD4 glycoprotein is required for T-cell function and development. Here we define the transcriptional control elements in the CD4 locus that convey CD(4+)-specific expression of a marker gene in transgenic mice. Using nuclear run-on experiments, we have determined that the major mechanism for CD4 expression control during development is transcriptional. We have identified a developmental stage- and tissue-specific negative regulatory element in the first intron of the murine CD4 gene that has the characteristics of a transcriptional silencer. The CD4 silencer functions to inhibit marker gene expression at two different stages of T-cell development, as well as in non-T hematopoietic cells, and thus is the critical controlling element responsible for T-cell-specific, as well as developmental- and subclass-specific, expression.
CD4糖蛋白的适当表达是T细胞功能和发育所必需的。在此，我们确定了CD4基因座中的转录控制元件，这些元件在转基因小鼠中传递标记基因的CD(4 +)特异性表达。通过核转录实验，我们确定了发育过程中CD4表达控制的主要机制是转录调控。我们在小鼠CD4基因的第一个内含子中鉴定出一个发育阶段和组织特异性的负调控元件，它具有转录沉默子的特征。CD4沉默子在T细胞发育的两个不同阶段以及非T造血细胞中发挥作用，抑制标记基因的表达，因此是负责T细胞特异性以及发育和亚类特异性表达的关键控制元件。
