Duncan D D, Adlam M, Siu G
Department of Microbiology, Columbia University, College of Physicians and Surgeons, New York 10032, USA.
Immunity. 1996 Mar;4(3):301-11. doi: 10.1016/s1074-7613(00)80438-0.
We and others have defined a transcriptional silencer critical for the proper expression of the CD4 gene at all stages of T cell development. In this report, we use biochemical techniques to identify three different factor-binding sites within the CD4 silencer, denoted sites I, II, and III. Using transgenic analyses, we determine that although all three factor-binding sites are important for silencer activity, there is significant redundancy in that the presence of either site II alone, or the combination of sites I and III permits silencer function. Thus, our data indicate that the mechanism of function of the CD4 silencer is extremely complex. Further biochemical analyses indicate that the factor binding to site II has the same sequence specificity as a factor binding to an E box site in the CD4 enhancer; thus, a member of the bHLH factor family may be important in mediating silencer function.
我们和其他研究人员已经确定了一种转录沉默子，它对于T细胞发育各个阶段CD4基因的正常表达至关重要。在本报告中，我们使用生化技术在CD4沉默子内鉴定出三个不同的因子结合位点，分别标记为位点I、II和III。通过转基因分析，我们确定尽管所有这三个因子结合位点对沉默子活性都很重要，但存在显著的冗余性，即单独存在位点II，或位点I和III的组合都能实现沉默子功能。因此，我们的数据表明CD4沉默子的功能机制极其复杂。进一步的生化分析表明，与位点II结合的因子与结合在CD4增强子中E盒位点的因子具有相同的序列特异性；因此，bHLH因子家族的一个成员可能在介导沉默子功能中起重要作用。
