Tissue specificity of a glucocorticoid-dependent enhancer in transgenic mice.

The glucocorticoid-responsive units (GRUs) of the rat tyrosine aminotransferase were associated with the regulatory sequences of a cellular gene expressed ubiquitously--that coding for the largest subunit of RNA polymerase II. In transient expression assays, glucocorticoid responsiveness of the hybrid regulatory regions depends on the spatial relationship and number of regulatory elements. Two parameters affect the ratio of induction by glucocorticoids: the basal level of the hybrid promoter that is affected by the RNA polymerase II regulatory sequences and the glucocorticoid-induced level that depends on the distance between the GRUs and the TATA box. A fully active glucocorticoid-responsive hybrid gene was used to generate transgenic mice. Results show that a composite regulatory pattern is obtained: ubiquitous basal expression characteristic of the RNA polymerase II gene and liver-specific glucocorticoid activation characteristic of the tyrosine aminotransferase GRUs. This result demonstrates that the activity of the tyrosine aminotransferase GRUs is cell-type-specific not only in cultured cells but also in the whole animal. IMAGES:

大鼠酪氨酸氨基转移酶的糖皮质激素响应元件（glucocorticoid-responsive units, GRUs）与一个泛在表达的细胞基因的调控序列相关联——该基因编码RNA聚合酶II（RNA polymerase II）的最大亚基。在瞬时表达实验中，嵌合调控区域的糖皮质激素响应性取决于调控元件的空间位置与数量。两类参数会影响糖皮质激素的诱导比率：一是受RNA聚合酶II调控序列影响的嵌合启动子基础表达水平，二是取决于GRUs与TATA盒之间距离的糖皮质激素诱导表达水平。研究人员利用具有完全活性的糖皮质激素响应嵌合基因制备了转基因小鼠。实验结果显示，该基因呈现出复合调控模式：兼具RNA聚合酶II基因的泛在基础表达特性，以及酪氨酸氨基转移酶GRUs所特有的肝脏特异性糖皮质激素激活特性。这一结果证实，酪氨酸氨基转移酶GRUs的细胞类型特异性不仅存在于培养细胞中，在整体动物体内同样成立。图片：