A regulatory element in the ApoCIII promoter that directs hepatic specific transcription binds to proteins in expressing and nonexpressing cell types.
A regulatory element in the ApoCIII promoter that directs hepatic specific transcription binds to proteins in expressing and nonexpressing cell types.
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DOI：
10.1016/s0021-9258(18)71596-2
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发表时间：
1989-09
期刊：
影响因子：
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通讯作者：
Todd Leff;Karen ReueQ;Agustin MelianV;Harry Culver;J. L. Breslow
中科院分区：
文献类型：
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作者：
Todd Leff;Karen ReueQ;Agustin MelianV;Harry Culver;J. L. Breslow
为了更好地理解的机制，确定细胞类型特异性基因表达，我们已经研究了转录活性的13个核苷酸的长序列元件，指定C3 P，位于apoCIII基因的启动子。我们证明，该元件是所需的高水平的apoCIII基因在肝细胞中的表达，并足以确定肝特异性表达时，引入到异源启动子。在肝细胞核提取物中鉴定了一种蛋白质，命名为AF-1，其结合该序列并推测负责其在肝细胞中的转录活性。尽管C3 P元件在HeLa细胞中没有活性，但在HeLa细胞核提取物中鉴定出具有C3 P结合特异性的蛋白质。虽然HeLa蛋白在其结合特异性和相对丰度方面与肝AF-1相似，但其分子量约为肝蛋白的两倍，表明它们是不同的蛋白质或相同蛋白质的不同形式。发现多种鼠组织类型，包括不表达apoCIII基因的那些，含有C3 P结合蛋白。我们的结论是，细胞类型特异性活性的C3 P元件是不是由于C3 P结合蛋白在非表达细胞的情况下，但在不同的细胞类型中的C3 P结合蛋白质的定性差异的结果。
To better understand the mechanisms that determine cell type-specific gene expression, we have examined the transcriptional activity of a 13-nucleotide long sequence element, designated C3P, located in the promoter of the apoCIII gene. We demonstrate that this element is required for high levels of apoCIII gene expression in hepatic cells and is sufficient to determine hepatic specific expression when introduced into a heterologous promoter. A protein was identified in hepatic cell nuclear extracts, designated AF-1, that binds to this sequence and is presumably responsible for its transcriptional activity in hepatic cells. Even though the C3P element is not active in HeLa cells, a protein with C3P binding specificity was identified in HeLa cell nuclear extracts. While the HeLa protein is similar to the hepatic AF-1 in its binding specificity and relative abundance, it has approximately twice the molecular weight of the hepatic protein, indicating that they are different proteins or different forms of the same protein. A variety of murine tissue types, including those that do not express the apoCIII gene, were found to contain C3P binding proteins. We conclude that the cell type-specific activity of the C3P element is not due to the absence of C3P binding proteins in nonexpressing cells but is the result of qualitative differences in C3P binding proteins in different cell types.