Kajimoto Y, Kawamori R, Watada H, Kamada T
First Department of Medicine, Osaka University School of Medicine.
Nihon Rinsho. 1994 Oct;52(10):2535-43.
Production of insulin is stringently restricted to the beta cells of the endocrine pancreas. The major mechanism directing this specificity operates at the level of transcription. Previous studies have demonstrated that the tissue specificity in the insulin gene expression results from the cell-specific activity of its 5'-flanking enhancer/promoter, which limits the expression of a linked gene to the beta cell in tissue culture and transgenic mouse. Deletion, mutation, DNase I foot-printing, and gel-shift analyses revealed the presence of multiple cis-acting motifs. A set of positive and, possibly, negative trans-acting factors that are found in insulin-producing and noninsulin producing cells bind to these cis-acting elements and thus regulate transcription. Included among those are IEB (E-box)-binding IEF-1, a nuclear protein complex which consists of two basic helix-loop-helix proteins, and CT-box (TAAT box)-binding IPF1/STF-1, a homeodomain-containing transcription factor.
胰岛素的产生严格局限于内分泌胰腺的β细胞。决定这种特异性的主要机制在转录水平起作用。先前的研究表明,胰岛素基因表达中的组织特异性源于其5'侧翼增强子/启动子的细胞特异性活性,这在组织培养和转基因小鼠中将一个连接基因的表达限制在β细胞中。缺失、突变、DNase I足迹分析和凝胶迁移分析揭示了多个顺式作用基序的存在。在产生胰岛素和不产生胰岛素的细胞中发现的一组正向以及可能的负向反式作用因子与这些顺式作用元件结合,从而调节转录。其中包括结合IEB(E盒)的IEF-1,这是一种核蛋白复合物,由两种碱性螺旋-环-螺旋蛋白组成,以及结合CT盒(TAAT盒)的IPF1/STF-1,这是一种含同源结构域的转录因子。