Transcription factor AP-2 regulates expression of the dopamine beta-hydroxylase gene.
Transcription factor AP-2 regulates expression of the dopamine beta-hydroxylase gene.
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转录因子 AP-2 调节多巴胺 β-羟化酶基因的表达。
DOI：
10.1046/j.1471-4159.1995.65020510.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
Lewis,E
中科院分区：
文献类型：
--
作者：
Greco,D;Zellmer,E;Zhang,Z;Lewis,E
编码神经递质生物合成酶多巴胺β羟化酶（DBH）的基因的表达以组织特异性模式进行调节，转录受环境刺激的影响。使用大鼠DBH基因的启动子近端区域和SHSY-5 Y神经母细胞瘤细胞的核提取物，鉴定了与含有转录因子AP-2识别位点的寡核苷酸竞争的DNA-蛋白质复合物。DNA酶足迹分析确定了DBH启动子的-136和-115之间的AP-2结合位点。该AP-2位点的突变导致基础报告基因表达降低7倍，但保留了第二信使刺激活性。将AP-2表达载体和DBH启动子-报告基因构建体共转染到培养的细胞中，导致报告基因表达的六倍刺激，证明AP-2能够反式激活DBH启动子。这些结果确定了大鼠DBH基因上的一个新的调控元件，并表明AP-2位点在维持DBH转录的基础水平中发挥作用。
Expression of the gene encoding the neurotransmitter biosynthetic enzyme dopamine β‐hydroxylase (DBH) is regulated in a tissue‐specific pattern, and transcription is influenced by environmental stimuli. Using the promoter proximal region of the rat DBH gene and nuclear extracts from SHSY‐5Y neuroblastoma cells, a DNA‐protein complex was identified that is competitive with oligonucleotides containing the recognition site of transcription factor AP‐2. DNase footprint analysis identified an AP‐2 binding site between −136 and −115 of the DBH promoter. Mutation of that AP‐2 site results in a sevenfold reduction of basal reporter gene expression, but second messenger‐stimulated activity is retained. Cotransfection of an AP‐2 expression vector and a DBH promoter‐reporter construct into cultured cells results in a sixfold stimulation of reporter gene expression, demonstrating the ability of AP‐2 totrans‐activate the DBH promoter. These results identify a new regulatory element on the rat DBH gene and suggest that the AP‐2 site plays a role in maintaining basal levels of DBH transcription.