Esposito C, Miccadei S, Saiardi A, Civitareale D
Istituto di Medicina Sperimentale, CNR, Viale C. Marx 15, 00137 Roma, Italy.
Biochem J. 1998 Apr 1;331 ( Pt 1)(Pt 1):37-40. doi: 10.1042/bj3310037.
In this study we report on a novel natural target of the paired domain transcription factor PAX 8 in the enhancer element of the human thyroperoxidase gene, one of the most important thyroid differentiation markers. It is the primary enzyme involved in thyroid hormone synthesis and PAX 8 has been previously identified as an activating factor of the rat thyroperoxidase gene promoter. In vitro, PAX 8 binds a cis element of the human enhancer and its exogenous expression induces the enhancer activity in co-transfection experiments in Cos-7 cells. When mutated at this binding site, the enhancer is no longer activated by PAX 8. Our finding strengthens the PAX 8 role in the maintenance of thyroid differentiation and in particular in the tissue-specific thyroperoxidase gene expression.
在本研究中，我们报告了配对结构域转录因子PAX 8在人类甲状腺过氧化物酶基因增强子元件中的一个新的天然靶点，甲状腺过氧化物酶基因是最重要的甲状腺分化标志物之一。它是参与甲状腺激素合成的主要酶，PAX 8先前已被鉴定为大鼠甲状腺过氧化物酶基因启动子的激活因子。在体外，PAX 8与人增强子的一个顺式元件结合，其外源性表达在Cos-7细胞的共转染实验中诱导增强子活性。当该结合位点发生突变时，增强子不再被PAX 8激活。我们的发现强化了PAX 8在维持甲状腺分化，特别是在组织特异性甲状腺过氧化物酶基因表达中的作用。
