Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements.

A Sanchez-Pacheco; T Palomino; A Aranda

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Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements.

机译：通过干扰启动子增强子元件，甲状腺激素对垂体特异性转录因子GHF-1 / Pit-1表达的负调节。

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Expression of the growth hormone gene is due to the presence of the pituitary-specific transcription factor GHF-1/Pit-1. The action of the thyroid hormone T3 is mediated by nuclear receptors that regulate transcription by interaction with DNA elements located near promoters of the regulated genes. In this study, we show that T3 inhibits expression of the GHF-1/Pit-1 gene in rat pituitary GH4C1 cells by a novel mechanism that involves transcriptional interference with other regulatory elements of the promoter. Sequences between bp -90 and -200 of the rat GHF-1/Pit-1 gene which do not contain a hormone response element but contain two cyclic AMP-responsive elements mediate most of the repressive effect of T3. The hormone reduces basal levels of GHF-1/Pit-1 promoter activity and antagonizes its response to cyclic AMP and the tumor promoter TPA (12-O-tetradecanoylphorbol-13-acetate). A similar repression is found with a heterologous promoter that contains four copies of the cyclic AMP-responsive element motif. This regulation provides a novel example of the cross-talk between the thyroid hormone receptor and the signal transduction pathways used by different hormones and growth factors. Additionally, T3 interferes with in vitro binding of GHF-1/Pit-1 to a positive autoregulatory element located at bp -45 to -63 and has a detectable inhibitory effect on the activity of a promoter construct which extends to bp -90 of 5'-flanking DNA. The regulation of the transcription factor provides a novel example of negative transcriptional regulation by thyroid hormones.

机译：生长激素基因的表达归因于垂体特异性转录因子GHF-1 / Pit-1的存在。甲状腺激素T3的作用由核受体介导，核受体通过与位于受调控基因启动子附近的DNA元素相互作用来调节转录。在这项研究中，我们表明T3通过一种涉及启动子其他调控元件转录干扰的新机制抑制了大鼠垂体GH4C1细胞中GHF-1 / Pit-1基因的表达。大鼠GHF-1 / Pit-1基因的bp -90至-200之间的序列不包含激素反应元件，但包含两个环状AMP反应元件，可介导T3的大部分抑制作用。该激素可降低GHF-1 / Pit-1启动子活性的基础水平，并拮抗其对环状AMP和肿瘤启动子TPA（12-O-十四烷酰佛波醇13-乙酸盐）的反应。对于含有四个拷贝的环状AMP-应答元件基序的异源启动子，发现了类似的抑制。该法规提供了甲状腺激素受体与不同激素和生长因子所使用的信号转导途径之间串扰的新例子。此外，T3会干扰GHF-1 / Pit-1与位于bp -45至-63的阳性自动调节元件的体外结合，并且对启动子构建体的活性具有可检测到的抑制作用，该构建体延伸至bp -90为5 '侧翼DNA。转录因子的调控为甲状腺激素的负转录调控提供了一个新的例子。

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《Molecular and Cellular Biology》 |1995年第11期|共9页
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A Sanchez-Pacheco; T Palomino; A Aranda;
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1. Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements. [J] . A Sanchez-Pacheco, T Palomino, A Aranda Molecular and Cellular Biology . 1995,第11期

机译：通过干扰启动子增强子元件，甲状腺激素对垂体特异性转录因子GHF-1 / Pit-1表达的负调节。
2. Ligand-dependent, Pit-1/growth hormone factor-1 (GHF-1)-independent transcriptional stimulation of rat growth hormone gene expression by thyroid hormone receptors in vitro. [J] . C S Suen, W W Chin Molecular and Cellular Biology . 1993,第3期

机译：配体依赖性，Pit-1 /生长激素因子-1（GHF-1）依赖性转录刺激大鼠甲状腺激素受体对大鼠生长激素基因表达的影响。
3. Interaction of Ets-1 and the POU-homeodomain protein GHF-1/Pit-1 reconstitutes pituitary-specific gene expression. [J] . A P Bradford, C Wasylyk, B Wasylyk, Molecular and Cellular Biology . 1997,第3期

机译：Ets-1和POU同源结构域蛋白GHF-1 / Pit-1的相互作用重建了垂体特异性基因表达。
4. Regulation of Genes Involved in Lipid Homeostasis and the Pathogenesis of Atherosclerosis: The Role of Promoters, Enhancers, Hormone Nuclear Receptors and Auxiliary Factors in Apolipoprotein Gene Regulation [C] . Vassilis Zannis, Eleoi Zanni, Dimitris Kardassis NATO Advanced Study Institute on Vascular Endothelium : Mechanisms of Cell Signaling . 1999

机译：调节患有脂质稳态的基因和动脉粥样硬化的发病机制：启动子，增强剂，激素核受体和载脂蛋白基因调控中的辅助因子的作用
5. Positive and negative regulation of neuroendocrine gene expression by zinc finger transcription factors: Identification of a negative retinoic acid response element in the rat oxytocin promoter, and the cloning of a novel factor binding a conserved element critical for effective expression of the growth hormone gene [D] . Lipkin, Steven Monroe 1993

机译：锌指转录因子对神经内分泌基因表达的正向和负向调节：鉴定大鼠催产素启动子中的视黄酸阴性反应元件，并克隆与保守元件结合的新型因子，该元件对于生长激素基因的有效表达至关重要
6. Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements. [O] . A Sanchez-Pacheco, T Palomino, A Aranda 1995

机译：通过干扰启动子增强子元件甲状腺激素对垂体特异性转录因子GHF-1 / Pit-1表达的负调节。
7. Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements. [O] . Sanchez-Pacheco, A, Palomino, T, Aranda, A 1995

机译：通过干扰启动子增强子元件，甲状腺激素对垂体特异性转录因子GHF-1 / Pit-1表达的负调节。

Negative regulation of expression of the pituitary-specific transcription factor GHF-1/Pit-1 by thyroid hormones through interference with promoter enhancer elements.

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