Majello B, Arcone R, Toniatti C, Ciliberto G
Dipartimento di Biochimica e Biotecnologie Mediche, University of Naples, Italy.
EMBO J. 1990 Feb;9(2):457-65. doi: 10.1002/j.1460-2075.1990.tb08131.x.
Transcription of the human C-reactive protein (CRP) gene is induced by interleukin-6 (IL-6) during acute inflammation. Important information for inducible CRP expression is located within the 90 bases preceding the transcriptional start site. We show that the CRP promoter contains two adjacent binding sites (beta and alpha) that interact with at least two hepatocyte-specific nuclear proteins, H-APF-1 and H-APF-2. Point mutations that abolish or reduce binding drastically affect the level of CRP gene expression. Binding to beta is identical when extracts from uninduced or IL-6-induced Hep3B cells are used. On the contrary, both quantitative and qualitative changes in the alpha binding can be detected with extracts from uninduced cells or from cells treated with IL-6 or IL-6 + cycloheximide. A synthetic promoter based on the multimerization of the beta-binding domain, but not of the alpha-domain, is highly inducible when transfected in hepatoma cells. These results are discussed in relation to the structure of the promoter region of other acute phase inducible genes.
在急性炎症期间，人C反应蛋白（CRP）基因的转录由白细胞介素-6（IL-6）诱导。可诱导CRP表达的重要信息位于转录起始位点之前的90个碱基内。我们发现CRP启动子包含两个相邻的结合位点（β和α），它们与至少两种肝细胞特异性核蛋白H-APF-1和H-APF-2相互作用。消除或减少结合的点突变会极大地影响CRP基因的表达水平。当使用未诱导或IL-6诱导的Hep3B细胞提取物时，与β的结合是相同的。相反，从未诱导细胞或用IL-6或IL-6 +环己酰亚胺处理的细胞提取物中可检测到α结合的定量和定性变化。基于β结合域而非α域多聚化的合成启动子在转染到肝癌细胞中时具有高度可诱导性。结合其他急性期可诱导基因启动子区域的结构对这些结果进行了讨论。
