Characterization of tissue-specific transcription by the human synapsin I gene promoter.
Characterization of tissue-specific transcription by the human synapsin I gene promoter.
复制标题
人突触蛋白 I 基因启动子的组织特异性转录的表征。
DOI：
10.1073/pnas.88.8.3431
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发表时间：
1991
影响因子：
11.1
通讯作者：
Südhof,TC
中科院分区：
文献类型：
--
作者：
Thiel,G;Greengard,P;Südhof,TC
突触素Ia和突触素Ib是由单个基因差异剪接而来的丰富的突触囊泡蛋白。为了确定控制突触素Ia/b神经元表达的调控元件，我们对人突触素I基因的启动子区域进行了功能分析。构建了突触素I基因与细菌基因氯霉素乙酰转移酶融合的2kb 5‘侧翼序列的杂合基因，并将其导入12种不同的神经细胞和非神经细胞系。总的来说，嵌合报告基因的表达与突触素I的内源性表达在不同的神经元细胞系中表现出很好的相关性，而在所有被研究的非神经元细胞系中，其转录水平都很低。猴病毒40增强子的加入促进了非组织特异性表达。突触素I启动子的缺失突变显示存在正负序列元件。在神经细胞和非神经细胞系中引导报告基因表达的一个基本(构成)启动子被定位在-115到+47区域。从-422到-22的启动子区域含有阳性元件，与单纯疱疹病毒胸苷激酶启动子融合后，可增强其在PC12和神经母细胞瘤细胞中的转录，但在中国仓鼠卵巢细胞中不能。
Synapsin Ia and synapsin Ib are abundant synaptic vesicle proteins that are derived by differential splicing from a single gene. To identify control elements directing the neuronal expression of synapsins Ia/b, we functionally analyzed the promoter region of the human synapsin I gene. A hybrid gene was constructed containing 2 kilobases of 5' flanking sequence from the synapsin I gene fused to the bacterial gene chloramphenicol acetyltransferase and transfected into 12 different neuronal and nonneuronal cell lines. In general, expression of the chimeric reporter gene showed excellent correlation with endogenous expression of synapsin I in different neuronal cell lines, whereas transcription was low in all nonneuronal cell lines examined. The addition of the simian virus 40 enhancer promoted non-tissue-specific expression. Deletion mutagenesis of the synapsin I promoter revealed the presence of positive and negative sequence elements. A basal (constitutive) promoter that directs reporter gene expression in neuronal and nonneuronal cell lines was mapped to the region -115 to +47. The promoter region from -422 to -22 contains positive elements that upon fusion with the herpes simplex virus thymidine kinase promoter potentiate its transcription in PC12 and neuroblastoma cells but not in Chinese hamster ovary cells.