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小鼠髓鞘碱性蛋白基因的核心启动子在体外调控脑特异性转录。

Core promoter of the mouse myelin basic protein gene governs brain-specific transcription in vitro.

作者信息

Tamura T, Sumita K, Hirose S, Mikoshiba K

机构信息

Division of Behavior and Neurobiology, National Institute for Basic Biology, Okazaki, Japan.

出版信息

EMBO J. 1990 Oct;9(10):3101-8. doi: 10.1002/j.1460-2075.1990.tb07507.x.

Abstract

The core promoter of the mouse myelin basic protein (MBP) gene from -36 to +12 was preferentially transcribed in brain nuclear extracts. Both the TATA at -34 and downstream elements to +12 were required for efficient, accurate and brain-specific transcription. From brain and liver nuclear extracts, we have partially purified the general transcription factor TFIID. The partially purified fractions contained TATA element binding factors of the MBP promoter as well as adenovirus major late promoter (MLP). The tissue-derived TFIID was functionally exchangeable for the HeLa TFIID, and directed transcription from the MLP. Surprisingly, the brain TFIID activated transcription from the MBP core promoter while the liver TFIID did to a much lesser extent. Exchange of the TATA-containing short DNA stretch to the MBP core promoter for a corresponding region of the mouse albumin promoter or MLP abolished the brain specificity. We found that several tissue-specific promoters other than MBP, such as mouse neurofilament and human alpha-1-antitrypsin promoters were also transcribed much more efficiently by the brain and liver TFIID, respectively. We suggest that different tissues contain functionally non-equivalent TFIID or TFIID-like activities.

摘要

小鼠髓鞘碱性蛋白(MBP)基因从-36至+12的核心启动子在脑细胞核提取物中优先转录。-34处的TATA盒和至+12的下游元件对于高效、准确且脑特异性的转录都是必需的。我们从脑和肝细胞核提取物中部分纯化了通用转录因子TFIID。部分纯化的组分包含MBP启动子以及腺病毒主要晚期启动子(MLP)的TATA元件结合因子。组织来源的TFIID在功能上可与HeLa细胞的TFIID互换,并指导来自MLP的转录。令人惊讶的是,脑TFIID激活了MBP核心启动子的转录,而肝TFIID的激活程度要小得多。将含TATA的短DNA片段从MBP核心启动子换成小鼠白蛋白启动子或MLP的相应区域,消除了脑特异性。我们发现,除MBP外,其他一些组织特异性启动子,如小鼠神经丝和人α-1-抗胰蛋白酶启动子,分别也能被脑和肝TFIID更高效地转录。我们认为不同组织含有功能不等同的TFIID或TFIID样活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6839/552037/8a9810273acb/emboj00237-0083-a.jpg

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