Wirth T, Baltimore D
Whitehead Institute for Biomedical Research, Cambridge, MA 02142.
EMBO J. 1988 Oct;7(10):3109-13. doi: 10.1002/j.1460-2075.1988.tb03177.x.
Enhancers and promoters, cis-acting regulators of mammalian gene expression, are modular units containing multiple short binding sites for specific trans-acting transcription factors. To investigate if factors binding to enhancer sequences are functionally different from promoter-binding factors, we asked if a short DNA sequence element in the immunoglobulin kappa (kappa) light chain enhancer that binds to the nuclear factor NF-kappa B could also serve as a functional promoter element. A synthetic oligonucleotide containing this binding site was placed in either orientation upstream of the beta-globin TATA-element. In myeloma cells, the NF-kappa B binding site efficiently directed transcription. The promoter activity was directly correlated with the presence of the nuclear factor NF-kappa B: there was no transcription in fibroblasts or in unstimulated pre-B cells where the factor was absent. Transcription could be stimulated in pre-B cells by treatments known to activate NF-kappa B. Thus, the same nuclear factor can act as a positive activator of both enhancer and promoter function, suggesting that the two functions involve similar events in the transcription process.
增强子和启动子是哺乳动物基因表达的顺式作用调节元件，是包含多个特异性反式作用转录因子短结合位点的模块化单元。为了研究与增强子序列结合的因子在功能上是否与启动子结合因子不同，我们探究了免疫球蛋白κ轻链增强子中与核因子NF-κB结合的短DNA序列元件是否也能作为功能性启动子元件。将含有该结合位点的合成寡核苷酸以任一方向置于β-珠蛋白TATA元件的上游。在骨髓瘤细胞中，NF-κB结合位点有效地指导转录。启动子活性与核因子NF-κB的存在直接相关：在该因子缺失的成纤维细胞或未受刺激的前B细胞中没有转录。已知激活NF-κB的处理可在原B细胞中刺激转录。因此，同一核因子可作为增强子和启动子功能的正激活剂，这表明这两种功能在转录过程中涉及相似的事件。
