Levy D E, Kessler D S, Pine R, Reich N, Darnell J E
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
Genes Dev. 1988 Apr;2(4):383-93. doi: 10.1101/gad.2.4.383.
Human alpha- and beta-interferons (IFNs) stimulate rapid but transient increases in transcription from a set of previously quiescent genes. Protein synthesis is not required for initial stimulation, but duration of the response is limited to a few hours by a process requiring synthesis of new proteins. An IFN-stimulated response element (ISRE) was identified 5' to an inducible gene by deletion analysis and point mutagenesis, and sequence comparisons with other promoters defined the consensus element YAGTTTC(A/T)YTTTYCC. Two classes of IFN-inducible nuclear factors were found that bind to the ISRE. The most rapidly induced factor appeared without new protein synthesis, whereas a second factor required active protein synthesis for its appearance and maintenance. The kinetics of appearance and loss of these binding activities correlate with the activation and repression of IFN-stimulated genes. These different IFN-activated or induced factors may bind sequentially to the same essential promoter element to first increase and then repress transcription.
人α-和β-干扰素（IFN）可刺激一组先前静止的基因转录迅速但短暂增加。初始刺激不需要蛋白质合成，但通过需要合成新蛋白质的过程，反应持续时间限制在几个小时。通过缺失分析和点突变，在一个可诱导基因的5'端鉴定出一个IFN刺激反应元件（ISRE），与其他启动子的序列比较确定了共有元件YAGTTTC(A/T)YTTTYCC。发现两类IFN诱导的核因子与ISRE结合。诱导最快的因子在没有新蛋白质合成的情况下出现，而第二个因子的出现和维持需要活跃的蛋白质合成。这些结合活性出现和消失的动力学与IFN刺激基因的激活和抑制相关。这些不同的IFN激活或诱导因子可能依次与相同的必需启动子元件结合，以先增加然后抑制转录。
