The roles of CRE, TRE, and TRE-adjacent S1 nuclease sensitive element in the regulation of tyrosine hydroxylase gene promoter activity by angiotensin II.
The roles of CRE, TRE, and TRE-adjacent S1 nuclease sensitive element in the regulation of tyrosine hydroxylase gene promoter activity by angiotensin II.
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CRE、TRE 和 TRE 相邻 S1 核酸酶敏感元件在血管紧张素 II 调节酪氨酸羟化酶基因启动子活性中的作用。
DOI：
10.1046/j.1471-4159.1996.67010026.x
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发表时间：
1996
影响因子：
4.7
通讯作者：
Stachowiak,MK
中科院分区：
文献类型：
--
作者：
Kim,EL;Esparza,FM;Stachowiak,MK
通过将酪氨酸羟化酶启动子-荧光素酶构建体转染到培养的牛肾上腺髓质细胞中，检查了血管紧张素 II 介导酪氨酸羟化酶基因激活的顺式元件。血管紧张素 II 反应元件位于 -54/+25-bp 和 -269/-55-bp 启动子区域内，并分别被鉴定为环状 AMP (CRE) 和 12-O-十四烷酰佛波醇 13-乙酸酯反应元件 (TRE) 样序列。与 CRE 不同，TRE 还支持基础启动子活性。减少血管紧张素 II 刺激的 TRE 或 CRE 突变消除了核蛋白与这些元素的体外结合，表明形成 CRE 和 TRE 诱导复合物的蛋白质可能介导血管紧张素 II 刺激。 TRE 与二元对称元素相邻。这两个位点形成一个共同的调节单元，其中二元对称元件充当 TRE 位点的阻遏物。分离的二分体对称元件在体外不结合核蛋白。在超螺旋 DNA 中，它表现出 S1 核酸酶敏感性，并被 DNA 十字形特异性抗体识别，这与与 TRE 重叠的十字形结构的挤出一致。消除十字形形成的突变与抑制活性的丧失相关。我们提出了一种酪氨酸羟化酶基因调控的新模型，其中 TRE 的功能通过相邻 DNA 的结构转变进行调节。
Theciselements mediating activation of the tyrosine hydroxylase gene by angiotensin II were examined by transfecting tyrosine hydroxylase promoter‐luciferase constructs into cultured bovine adrenal medullary cells. Angiotensin II‐responsive elements are located within −54/+25‐bp and −269/−55‐bp promoter regions and were identified, respectively, as cyclic AMP (CRE)‐ and 12‐O‐tetradecanoylphorbol 13‐acetate responsive element (TRE)‐like sequences. Unlike CRE, TRE also supports basal promoter activity. Mutations of TRE or CRE that reduced angiotensin II stimulation abolished in vitro binding of nuclear proteins to those elements, suggesting that proteins forming CRE‐ and TRE‐inducible complexes may mediate angiotensin II stimulation. The TRE is adjacent to a dyad symmetry element. Those two sites form a common regulatory unit in which the dyad symmetry element acts as a repressor of the TRE site. Isolated dyad symmetry element did not bind nuclear proteins in vitro. In supercoiled DNA it exhibited S1 nuclease sensitivity and was recognized by a DNA cruciform‐specific antibody consistent with the extrusion of a cruciform structure that overlaps with the TRE. A mutation that abolished formation of the cruciform correlated with a loss of repressor activity. We propose a novel model of tyrosine hydroxylase gene regulation in which functions of the TRE are modulated via structural transition in the adjacent DNA.