Sinclair A J, Lonigro R, Civitareale D, Ghibelli L, Di Lauro R
European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Eur J Biochem. 1990 Oct 24;193(2):311-8. doi: 10.1111/j.1432-1033.1990.tb19339.x.
Thyroid-specific expression of the rat thyroglobulin gene is mediated by transcriptional control. Sufficient DNA sequence information to confer thyroid-specific expression to a heterologous gene is contained between positions -168 and +39. DNA-binding studies have demonstrated that this region interacts with two thyroid-specific factors (TTF-1 and TTF-2), and a ubiquitous factor (UFA). Here we have characterized three elements within the promoter, A, K, and C, which are important for promoter activity in thyroid cells. We have shown by mutational analysis that the interaction of TTF-1 with the A and C regions. UFA with the A region, and TTF-2 with the K region are required for full promoter activity. The complex interactions in the A region can be replaced by the substitution of the UFA/TTF-1-binding site with a high-affinity TTF-1 binding site. There is a correlation between the presence of TTF-1 and TTF-2 DNA-binding activities and the expression of thyroglobulin, which implies that the mechanism restricting thyroglobulin expression to thyroid cells is mediated through the control of the expression, or the activity, of TTF-1 and TTF-2.
大鼠甲状腺球蛋白基因的甲状腺特异性表达是由转录控制介导的。赋予异源基因甲状腺特异性表达的足够DNA序列信息包含在-168至+39位之间。DNA结合研究表明，该区域与两种甲状腺特异性因子（TTF-1和TTF-2）以及一种普遍存在的因子（UFA）相互作用。在此，我们鉴定了启动子内的三个元件A、K和C，它们对甲状腺细胞中的启动子活性很重要。我们通过突变分析表明，TTF-1与A和C区域的相互作用、UFA与A区域的相互作用以及TTF-2与K区域的相互作用是启动子完全活性所必需的。A区域中的复杂相互作用可以通过用高亲和力的TTF-1结合位点取代UFA/TTF-1结合位点来替代。TTF-1和TTF-2 DNA结合活性的存在与甲状腺球蛋白的表达之间存在相关性，这意味着将甲状腺球蛋白表达限制在甲状腺细胞中的机制是通过控制TTF-1和TTF-2的表达或活性来介导的。
