Tbx19, a tissue-selective regulator of POMC gene expression

Tbx19, a tissue-selective regulator of POMC gene expression
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DOI:
10.1073/pnas.141234898
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发表时间:
2001-07-17
影响因子:
11.1
通讯作者:
Rosenfeld, MG
Rosenfeld, MG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu, JX;Lin, CJ;Rosenfeld, MG

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垂体细胞类型在时间和空间上以一种特定的方式出现,以响应瞬时信号梯度诱导的转录因子的组合作用。表达前阿片黑素皮质素(POMC)基因的两种类型的垂体细胞,即产生促肾上腺皮质激素的前袍皮质细胞和产生黑素细胞刺激素(MSHα)的中间叶促黑素细胞,其关键转录决定因素尚不清楚。在这里,我们报道了T-box基因家族的一个成员Tbx19,它从e11.5开始只在吻侧腹间脑和脑垂体腺中表达,它标记了随后将表达POMC基因的垂体细胞,并能够改变腹侧细胞类型的进展,并在吻端细胞中诱导促肾上腺皮质激素。提示Tbx19可以激活POMC基因的表达,抑制α-糖蛋白亚基和促甲状腺激素β启动子的表达,并依赖于协同转录因子的存在。
Pituitary cell types arise in a temporally and spatially specific fashion, in response to combinatorial actions of transcription factors induced by transient signaling gradients. The critical transcriptional determinants of the two pituitary cell types that express the pro-opiomelanocortin (POMC) gene, the anterior robe corticotropes, producing adrenocorticotropin, and the intermediate lobe melanotropes, producing melanocyte-stimulating hormone (MSH alpha), have remained unknown. Here, we report that a member of the T-box gene family, Tbx19 which is expressed only in the rostral ventral diencephalon and pituitary gland, commencing on e11.5, marks pituitary cells that will subsequently express the POMC gene and is capable of altering progression of ventral cell types and inducing adrenocorticotropin in rostral tip cells. It is suggested that Tbx19, depending on the presence of synergizing transcription factors, can activate POMC gene expression and repress the alpha glycoprotein subunit and thyroid-stimulating hormone beta promoters.