Sasaki Shigekazu, Matsushita Akio, Kuroda Go, Nakamura Hiroko M, Oki Yutaka, Suda Takafumi
Hamamatsu University School of Medicine, Shizuoka, Japan.
Hamamatsu University School of Medicine, Shizuoka, Japan.
Vitam Horm. 2018;106:97-127. doi: 10.1016/bs.vh.2017.06.006. Epub 2017 Aug 18.
Thyroid hormone (T3) activates (positive regulation) or represses (negative regulation) target genes at the transcriptional level. The molecular mechanism of the former has been elucidated in detail; however, the mechanism for negative regulation has not been established. The best example of the gene that is negatively regulated by T3 is the thyrotropin (thyroid-stimulating hormone) β subunit (TSHβ) gene. Analogous to the T3-responsive element (TRE) in positive regulation, a negative TRE (nTRE) has been postulated in the TSHβ gene. However, TSHβ promoter analysis, performed in the presence of transcription factors Pit1 and GATA2, which are determinants of thyrotroph differentiation in the pituitary, revealed that the nTRE is dispensable for inhibition by T3. We propose a tethering model in which the T3 receptor is tethered to GATA2 via protein-protein interaction and inhibits GATA2-dependent transactivation of the TSHβ gene in a T3-dependent manner.
甲状腺激素（T3）在转录水平激活（正调控）或抑制（负调控）靶基因。前者的分子机制已得到详细阐明；然而，负调控机制尚未确立。受T3负调控的基因的最佳例子是促甲状腺激素（甲状腺刺激激素）β亚基（TSHβ）基因。与正调控中的T3反应元件（TRE）类似，TSHβ基因中已假定存在负TRE（nTRE）。然而，在垂体中促甲状腺细胞分化的决定因素转录因子Pit1和GATA2存在的情况下进行的TSHβ启动子分析表明，nTRE对于T3的抑制作用并非必需。我们提出了一种拴系模型，其中T3受体通过蛋白质-蛋白质相互作用与GATA2拴系，并以T3依赖的方式抑制GATA2依赖的TSHβ基因反式激活。
