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首页> 外文期刊>DNA and Cell Biology >Myocyte-specific M-CAT and MEF-1 elements regulate G-protein gamma 3 gene (gamma3) expression in cardiac myocytes.
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Myocyte-specific M-CAT and MEF-1 elements regulate G-protein gamma 3 gene (gamma3) expression in cardiac myocytes.

机译：心肌细胞特异性M-CAT和MEF-1元素调节心肌细胞中G蛋白γ3基因（gamma3）的表达。

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摘要

Little is known regarding the mechanisms that control the expression of G-protein alpha, beta, and gamma subtypes. We have previously shown that the G-protein gamma(3) gene is expressed in the heart, brain, lung, spleen, kidney, muscle, and testis in mice. We have also reported that the G-protein gamma(3) subunit is expressed in rat cardiac myocytes, but not in cardiac fibroblasts. Other studies have shown that the gamma(3) subunit couples to the angiotensin A1A receptor in portal vein myocytes, and has been shown to mediate beta-adrenergic desensitization in cardiac myocytes treated with atorvastatin. In the present study, we evaluated G-protein gamma(3) promoter-luciferase reporter constructs in primary myocytes to identify key regulatory promoter regions. We identified two important regions of the promoter (upstream promoter region [UPR] and downstream promoter region [DPR]), which are required for expression in cardiac myocytes. We observed that removal of 48 bp in the UPR diminished gene transcription by 75%, and that the UPR contains consensus elements for myocyte-specific M-CAT and myocyte enhancer factor 1 (MEF-1) elements. The UPR and DPR share transcription factor elements for myocyte-specific M-CAT element. We observed that cardiac myocyte proteins bind to gamma(3) oligonucleotides containing transcription factor elements for myocyte-specific M-CAT and MEF-1. Myocyte-specific M-CAT proteins were supershifted with transcriptional enhancer factor-1 (TEF-1) antibodies binding to the gamma(3) M-CAT element, which is in agreement with reports showing that the M-CAT element binds the TEF-1 family of transcription factors. The 150 bp DPR contains three M-CAT elements, an INR element, an upstream stimulatory factor 1 element, and the transcription start site. We have shown that myocyte gamma(3) gene expression is regulated by myocyte-specific M-CAT and MEF-1 elements.
机译：关于控制G蛋白α，β和γ亚型表达的机制知之甚少。我们以前已经表明，G蛋白gamma（3）基因在小鼠的心脏，大脑，肺，脾脏，肾脏，肌肉和睾丸中表达。我们还报告了G蛋白gamma（3）亚基在大鼠心肌细胞中表达，但在心脏成纤维细胞中不表达。其他研究表明，γ（3）亚基与门静脉心肌细胞中的血管紧张素A1A受体偶联，并已显示出在用阿托伐他汀治疗的心肌细胞中介导β-肾上腺素能脱敏。在本研究中，我们评估了原代心肌细胞中的G蛋白gamma（3）启动子-荧光素酶报告基因构建物，以鉴定关键的调控启动子区域。我们确定了启动子的两个重要区域（上游启动子区域[UPR]和下游启动子区域[DPR]），这是在心肌细胞中表达所必需的。我们观察到，UPR中48 bp的去除使基因转录减少了75％，并且UPR包含针对肌细胞特异性M-CAT和肌细胞增强因子1（MEF-1）元素的共有元件。 UPR和DPR共享肌细胞特异性M-CAT元件的转录因子元件。我们观察到，心肌细胞蛋白与含有针对肌细胞特异性M-CAT和MEF-1的转录因子元件的gamma（3）寡核苷酸结合。肌细胞特异性M-CAT蛋白被与γ（3）M-CAT元素结合的转录增强因子-1（TEF-1）抗体超移位，这与报道显示M-CAT元素结合TEF- 1个转录因子家族。 150 bp DPR包含三个M-CAT元素，一个INR元素，一个上游刺激因子1元素和一个转录起始位点。我们已经表明，心肌细胞γ（3）基因表达受心肌细胞特异性M-CAT和MEF-1元素调控。

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