Mathey-Prevot B, Andrews N C, Murphy H S, Kreissman S G, Nathan D G
Division of Hematology Oncology, Children's Hospital, Boston MA 02115.
Proc Natl Acad Sci U S A. 1990 Jul;87(13):5046-50. doi: 10.1073/pnas.87.13.5046.
The human interleukin 3 (IL-3) promoter is comprised of several cis-acting DNA sequences that modulate T-cell expression of IL-3. These are located within 315 nucleotides upstream of the mRNA start site. Transient expression of reporter genes linked to serially deleted sequences of the IL-3 promoter has allowed mapping of two activator sequences and an interposed repressor sequence. The proximal regulatory region is specific to IL-3 and prerequisite for efficient transcription. Its effect is enhanced by a second, more distal activating sequence consisting of an AP-1 binding site. Between the two activators lies a transcriptional silencer, which is a potent repressor in the absence of the AP-1 site. DNA-nuclear protein binding experiments demonstrate specific complex formation within each of these functional regions. Thus, both positive and negative regulatory elements appear to control expression of the human IL-3 gene in activated T cells.
人白细胞介素3(IL-3)启动子由几个顺式作用DNA序列组成,这些序列调节IL-3在T细胞中的表达。它们位于mRNA起始位点上游315个核苷酸内。与IL-3启动子的串联缺失序列相连的报告基因的瞬时表达,使得两个激活序列和一个插入的抑制序列得以定位。近端调控区域对IL-3具有特异性,是高效转录的先决条件。其作用通过由AP-1结合位点组成的第二个更远端的激活序列而增强。在两个激活剂之间存在一个转录沉默子,在没有AP-1位点的情况下它是一种有效的抑制剂。DNA-核蛋白结合实验证明在这些功能区域中的每一个内都形成了特异性复合物。因此,正负调控元件似乎都在控制活化T细胞中人IL-3基因的表达。