对鼠 Pax8 启动子的功能分析揭示了其自身调控以及存在一种新的甲状腺特异性 DNA 结合活性。
Functional analysis of the murine Pax8 promoter reveals autoregulation and the presence of a novel thyroid-specific DNA-binding activity.
机构信息
IRGS, Biogem, Avellino, Italy.
出版信息
Thyroid. 2013 Apr;23(4):488-96. doi: 10.1089/thy.2012.0357. Epub 2013 Mar 18.
BACKGROUND
Organogenesis of the thyroid gland requires the Pax8 protein. Absence or reduction of Pax8 results in congenital hypothyroidism in animal models and humans, respectively. This study aims at elucidating the regulatory mechanism leading to the expression of Pax8 in thyroid cells.
METHODS
The murine Pax8 gene promoter was functionally dissected by mutagenesis and transfection in the thyroid cell line FRTL-5. Nuclear factors important for thyroid-specific gene expression were identified by DNA-binding assays.
RESULTS
We show that Pax8 binds to and controls the expression of its own promoter. Furthermore, we identify a novel, thyroid-specific, DNA-binding activity (denominated nTTF [for novel Thyroid Transcription Factor]) that recognizes a specific region of the Pax8 promoter.
CONCLUSIONS
The Pax8 promoter appears to be autoregulated, a feature that might be responsible for the haploinsufficiency displayed by this gene.
背景
甲状腺的发生需要 Pax8 蛋白。动物模型和人类中 Pax8 的缺失或减少分别导致先天性甲状腺功能减退症。本研究旨在阐明导致甲状腺细胞中 Pax8 表达的调节机制。
方法
通过在甲状腺细胞系 FRTL-5 中转染和突变，对小鼠 Pax8 基因启动子进行功能解析。通过 DNA 结合测定鉴定对甲状腺特异性基因表达重要的核因子。
结果
我们表明 Pax8 结合并控制其自身启动子的表达。此外，我们鉴定了一种新的、甲状腺特异性的 DNA 结合活性（命名为 nTTF [用于新的甲状腺转录因子]），它可以识别 Pax8 启动子的特定区域。
结论
Pax8 启动子似乎是自我调控的，这一特征可能是该基因表现出单倍不足的原因。
Zotero 插件