A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific and regulated expression in brown adipose tissue
A 211-bp enhancer of the rat uncoupling protein-1 (UCP-1) gene controls specific and regulated expression in brown adipose tissue
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DOI：
10.1042/bj3330243
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发表时间：
1998-07-15
影响因子：
4.1
通讯作者：
Ricquier, D
中科院分区：
文献类型：
--
作者：
Cassard-Doulcier, AM;Gelly, C;Ricquier, D
解偶联蛋白-1 基因在棕色脂肪组织 (BAT) 中独特表达，并受到动物冷暴露和交感神经系统的正向调节。分析先前鉴定的 211-bp 增强子的重要性 [Cassard-Doulcier, Gelly, Fox, Schrementi, Raimbault, Klaus, Forest, Bouillaud 和 Ricquier (1993) Mel.内分泌。 [7, 497-506] 在该基因的组织特异性表达中，使用氯霉素乙酰转移酶（CAT）基因作为报告基因产生转基因小鼠。带有单纯疱疹胸苷激酶 (TK) 启动子的对照转基因小鼠的十四个品系中，有一个在多个组织中微弱地表达 CAT 报告基因，而其他品系不表达 CAT。获得了八个携带211-bp增强子-TK转基因的创始人。在 6 个品系中，未检测到 CAT 表达。在一个品系中，CAT 的表达仅限于 BAT。在另一株系中，在 BAT 中发现了 CAT 的表达，在睾丸中也发现了较小程度的表达。此外，在这些细胞系中，在将小鼠暴露于寒冷中或用β-肾上腺素受体激动剂药物治疗后，观察到BAT中报告基因表达的显着且特异性的增加。这些结果表明，单独的 211 bp 增强子足以指导和限制 BAT 的表达。该增强子还介导基因对 β-肾上腺素能刺激的转录反应，尽管它不包含保守的 cAMP 反应元件。
The uncoupling protein-1 gene is uniquely expressed in brown adipose tissue (BAT) and is positively regulated by cold exposure of animals and the sympathetic nervous system. To analyse the importance of a previously identified 211-bp enhancer [Cassard-Doulcier, Gelly, Fox, Schrementi, Raimbault, Klaus, Forest, Bouillaud and Ricquier (1993) Mel. Endocrinol. 7, 497-506] in the tissue-specific expression of this gene, transgenic mice were generated using the chloramphenicol acetyltransferase (CAT) gene as a reporter gene. One out of fourteen lines of the control transgenic mice bearing the Herpes simplex thymidine kinase (TK) promoter expressed weakly the CAT reporter gene in several tissues, whereas the other lines did not express CAT. Eight founders bearing the 211-bp enhancer-TK transgene were obtained. In six lines, no expression of CAT was detected. In one line, the expression of CAT was restricted to BAT. In another line, the expression of CAT was found in BAT and, to a lesser extent, in testis. Moreover, in these lines a marked and specific increase in the expression of the reporter gene in BAT was observed either after exposure of mice to the cold or by treating them with a beta-adrenoceptor agonist drug. These results demonstrate that the 211-bp enhancer alone is sufficient to both direct and restrict expression to BAT. This enhancer also mediates the transcriptional response of the gene to beta-adrenergic stimulation, although it does not contain conserved cAMP response element.