Roffet P, Lopez S, Navarro S, Bandu M T, Coulombel C, Vignal M, Doly J, Vodjdani G
Laboratoire de Régulation de l'Expression des Gènes Eucaryotes, UPR 37-CNRS, UFR Biomédicale, Université, René Descartes, Paris, France.
Biochem J. 1996 Aug 1;317 ( Pt 3)(Pt 3):697-706. doi: 10.1042/bj3170697.
The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A multigenic family. In mouse L929 cells, the weak response of the gene's promoter to viral induction is due to a combination of both a point mutation in the virus responsive element (VRE) and the presence of negatively regulating sequences surrounding the VRE. In the distal part of the promoter, the negatively acting E1E2 sequence was delimited. This sequence displays an inhibitory effect in either orientation or position on the inducibility of a virus-responsive heterologous promoter. It selectively represses VRE-dependent transcription but is not able to reduce the transcriptional activity of a VRE-lacking promoter. In a transient transfection assay, an E1E2-containing DNA competitor was able to derepress the native Mu IFN-A11 promoter. Specific nuclear factors bind to this sequence; thus the binding of trans-regulators participates in the repression of the Mu IFN-A11 gene. The E1E2 sequence contains an IFN regulatory factor (IRF)-binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies supershift a major complex formed with nuclear extracts. The protein composing the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically related proteins in the complex. The Mu IFN-A11 gene is the first example within the murine IFN-A family, in which a distal promoter element has been identified that can negatively modulate the transcriptional response to viral induction.
小鼠干扰素 -A11（Mu IFN -A11）基因是IFN -A多基因家族的成员。在小鼠L929细胞中，该基因启动子对病毒诱导的弱反应是由于病毒反应元件（VRE）中的点突变以及VRE周围负调控序列的存在共同作用的结果。在启动子的远端，确定了负向作用的E1E2序列。该序列在任何方向或位置对病毒反应性异源启动子的诱导性均显示出抑制作用。它选择性地抑制VRE依赖性转录，但不能降低缺乏VRE的启动子的转录活性。在瞬时转染实验中，含E1E2的DNA竞争物能够解除对天然Mu IFN -A11启动子的抑制。特定的核因子与该序列结合；因此反式调节因子的结合参与了Mu IFN -A11基因的抑制。E1E2序列包含一个干扰素调节因子（IRF）结合位点。重组IRF2结合该序列，抗IRF2抗体使与核提取物形成的主要复合物发生超迁移。组成该复合物的蛋白质大小为50 kDa，表明复合物中存在IRF2或抗原相关蛋白。Mu IFN -A11基因是小鼠IFN -A家族中的首个例子，其中已鉴定出一个远端启动子元件，它可对病毒诱导的转录反应进行负向调节。
