The role of proximal-enhancer elements in the glucocorticoid regulation of carbamoylphosphate synthetase gene transcription from the upstream response unit
The role of proximal-enhancer elements in the glucocorticoid regulation of carbamoylphosphate synthetase gene transcription from the upstream response unit
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DOI：
10.1016/j.biochi.2005.02.015
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发表时间：
2005-11-01
期刊：
影响因子：
3.9
通讯作者：
Lamers, WH
中科院分区：
文献类型：
--
作者：
Schoneveld, OJLM;Gaemers, IC;Lamers, WH
作为尿素循环的一部分，氨甲酰磷酸合成酶（CPS）将由氨基酸催化剂产生的有毒氨转化为尿素。该基因的肝脏特异性和糖皮质激素依赖性表达涉及远端增强子、启动子近端增强子和最小启动子本身。当用糖皮质激素挑战时，氨甲酰磷酸合成酶基因的远端增强子中的糖皮质激素响应单元（GRU）仅在除了最小启动子之外还存在近端增强子的情况下才能激活基因表达。在这里，我们确定并验证了近端CPS增强子中的两个元件，它们参与GRU介导的糖皮质激素依赖性基因激活。形成所谓的GAGA盒和糖皮质激素反应元件（GRE）的富含嘌呤的延伸对于GRU的功效都是至关重要的，并且似乎构成激活启动子的启动子近端反应单元。因此，CPS基因的糖皮质激素反应依赖于远端和启动子近端反应单元的联合作用。(C)2005年，Elsevier SAS。All rights reserved.
As part of the urea cycle, carbamoylphosphate synthetase (CPS) converts toxic ammonia resulting from amino-acid catabolism into urea. Liver-specific and glucocorticoid-dependent expression of the gene involves a distal enhancer, a promoter-proximal enhancer, and the minimal promoter itself. When challenged with glucocorticoids, the glucocorticoid-responsive unit (GRU) in the distal enhancer of the carbamoylphosphate-synthetase gene can only activate gene expression if, in addition to the minimal promoter, the proximal enhancer is present. Here, we identify and characterise two elements in the proximal CPS enhancer that are involved in glucocorticoid-dependent gene activation mediated by the GRU. A purine-rich stretch forming a so-called GAGA-box and a glucocorticoid-response element (GRE) are both crucial for the efficacy of the GRU and appear to constitute a promoter-proximal response unit that activates the promoter. The glucocorticoid response of the CPS gene is, therefore, dependent on the combined action of a distal and a promoter-proximal response unit. (C) 2005 Elsevier SAS. All rights reserved.