Chang K C, Hansen E, Jaenicke T, Goldspink G, Butterworth P
Unit of Veterinary Molecular and Cellular Biology, Royal Veterinary College, University of London, UK.
Nucleic Acids Res. 1992 Apr 11;20(7):1669-74. doi: 10.1093/nar/20.7.1669.
Studies on the regulation of interferon (IFN) responsive genes have mainly been centred on the highly conserved IFN stimulated responsive elements (ISREs) which can mediate type I and II IFN inducibility. To date little is known about other functional cis-acting regulatory motifs in IFN responsive genes. We report here on the identification of a repressor element in the human MxA gene defined to a 19 base pair (bp) region which houses a 9 bp direct repeat. DNA-specific protein binding on this element is not affected by IFN treatment and is distinct from ISRE binding proteins. Remarkably, contrary to expectations, when the repressor element is multimerised and spliced, in either orientation, to a reporter gene it behaves like a functional, constitutive promoter. Positioning the multimerised element in front of the SV40 enhancerless promoter also led to enhanced expression. The same protein(s) seem to bind to both the single repressor element and its multimerised form. This discovery of phenotypic reversal on a repressor element via multimerisation may have important implications in vivo.
关于干扰素（IFN）反应基因调控的研究主要集中在高度保守的干扰素刺激反应元件（ISREs）上，这些元件可介导I型和II型干扰素的诱导作用。迄今为止，对于IFN反应基因中其他功能性顺式作用调控基序知之甚少。我们在此报告在人类MxA基因中鉴定出一个阻遏元件，该元件定位于一个包含9个碱基对直接重复序列的19个碱基对（bp）区域。该元件上的DNA特异性蛋白结合不受IFN处理的影响，且与ISRE结合蛋白不同。值得注意的是，与预期相反，当阻遏元件以任何方向多聚化并连接到报告基因时，它表现得像一个功能性的组成型启动子。将多聚化元件置于SV40无增强子启动子之前也导致表达增强。似乎相同的蛋白质与单个阻遏元件及其多聚化形式都结合。通过多聚化在阻遏元件上发现的表型逆转可能在体内具有重要意义。
