首页> 外文期刊>Molecular and Cellular Biology >The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression.
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The maf proto-oncogene stimulates transcription from multiple sites in a promoter that directs Purkinje neuron-specific gene expression.

机译:maf原癌基因在指导Purkinje神经元特异性基因表达的启动子中刺激多个位点的转录。

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L7 is expressed in all adult cerebellar Purkinje cells, although during development it appears in a stereotyped spatial and temporal pattern that is manifested as parasagittal domains of neurons. Mutations of the L7 promoter in transgenic mice have established that these domains represent functional compartments of Purkinje neurons. Therefore, it is hoped that by defining the transcriptional control of the L7 gene insights into the mechanisms that control functional fate and organization in the nervous system can be gained. Fragments of the L7 promoter were introduced into a selectable reporter gene in Saccharomyces cerevisiae, and these strains were used to select for cerebellar cDNAs encoding proteins that can bind to, and activate transcription from, these elements. This assay identified the c-Maf proto-oncogene as activating transcription from two sites in the L7 promoter. We did a functional domain analysis of vertebrate c-Maf based upon transcriptional activation in S. cerevisiae and showed the requirement for a transactivation domain, leucine zipper, and DNA-binding region in c-Maf. The c-Maf interaction site was mapped to the sequence G/TGG/CNG/TNCT CAGNN in the L7 promoter, which represents an atypical 12-O-tetradecanoate-13-acetate-responsive element-type Maf-responsive element. However, neither Fos nor Jun, either alone or in combination with each other or c-Maf, altered transcription from this element. In contrast, a Maf-related protein, Nrl, completely mimicked c-Maf actions. These data suggest that Maf may interact with additional basic-zipper proteins that determine a subtype of Maf-responsive element binding.
机译:L7在所有成年的小脑浦肯野细胞中都有表达,尽管在发育过程中它以定型的时空模式出现,表现为神经元的矢状旁突域。转基因小鼠中L7启动子的突变已确定这些结构域代表浦肯野神经元的功能区室。因此,希望通过定义L7基因的转录控制,可以深入了解控制神经系统功能命运和组织的机制。将L7启动子的片段引入酿酒酵母中的选择性报告基因中,并将这些菌株用于选择小脑cDNA,该小脑cDNA编码可结合这些元件并激活这些元件的转录的蛋白质。该测定法鉴定出c-Maf原癌基因可激活来自L7启动子中两个位点的转录。我们根据酿酒酵母中的转录激活作用对脊椎动物c-Maf进行了功能域分析,并显示了c-Maf中反式激活域,亮氨酸拉链和DNA结合区的需求。 c-Maf相互作用位点被映射到L7启动子中的序列G / TGG / CNG / TNCT CAGNN,该序列代表非典型的12-O-十四烷酸酯-13-乙酸酯响应元件类型的Maf响应元件。但是,无论是Fos还是Jun,单独或彼此结合或与c-Maf结合都不会改变该元件的转录。相反,Maf相关蛋白Nrl完全模仿c-Maf的作用。这些数据表明,Maf可能与其他决定Maf响应元件结合的亚型的碱性拉链蛋白相互作用。

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