Ikuyama S, Nawata H
Third Department of Internal Medicine, Kyushu University, Faculty of Medicine.
Nihon Rinsho. 1994 Apr;52(4):962-8.
TSH receptor (TSHR) is expressed almost exclusively in thyroid cells. The rat TSHR gene has a TATA-less, GC-rich promoter, with multiple transcriptional start sites. The minimal promoter region, sufficient for the basal promoter activity, thyroid-specific expression and negative regulation by TSH/cAMP signal, is located between -195 and -39 bp relative to the ATG start codon, and is highly conserved in the rat and human genes. This region comprises three important elements. First, a cAMP response element (CRE), which functions as a constitutive enhancer essential for the basal promoter activity. Second, tandem repeat sequences just 5' to the CRE, which are recognized by two distinct ssDNA-binding proteins. This element suppresses the function of the CRE, thus repressing the promoter activity. Third, a binding site for the thyroid-specific transcription factor TTF-1, which dictates thyroid-specific expression and negative regulation by TSH/cAMP of the gene. Thus, the expression of the TSHR gene is exquisitely regulated by these multiple factors in thyroid and non-thyroid cells.
促甲状腺激素受体（TSHR）几乎仅在甲状腺细胞中表达。大鼠TSHR基因有一个无TATA盒、富含GC的启动子，具有多个转录起始位点。对于基础启动子活性、甲状腺特异性表达以及TSH/cAMP信号的负调控而言，最小启动子区域位于相对于ATG起始密码子的-195至-39 bp之间，并且在大鼠和人类基因中高度保守。该区域包含三个重要元件。第一，一个环磷酸腺苷反应元件（CRE），其作为基础启动子活性所必需的组成型增强子发挥作用。第二，位于CRE上游5'端的串联重复序列，可被两种不同的单链DNA结合蛋白识别。该元件抑制CRE的功能，从而抑制启动子活性。第三，甲状腺特异性转录因子TTF-1的结合位点，它决定了该基因的甲状腺特异性表达以及TSH/cAMP对其的负调控。因此，TSHR基因的表达在甲状腺细胞和非甲状腺细胞中受到这些多种因素的精确调控。
