Regulation of rat insulin 1 gene expression: evidence for negative regulation in nonpancreatic cells.
Regulation of rat insulin 1 gene expression: evidence for negative regulation in nonpancreatic cells.
复制标题
大鼠胰岛素 1 基因表达的调节：非胰腺细胞负调节的证据。
DOI：
10.1073/pnas.83.10.3180
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发表时间：
1986
影响因子：
11.1
通讯作者：
Rutter,WJ
中科院分区：
文献类型：
--
作者：
Nir,U;Walker,MD;Rutter,WJ
Two cis-acting elements, the enhancer and the promoter, independently contribute to the cell-specific expression of the rat insulin 1 gene. The activities of these elements are presumably mediated by trans-acting factors. We have performed intracellular competition experiments that suggest the presence of a negative factor(s) that represses the enhancer activity in cells that do not express the insulin gene. In these experiments fibroblast cells (COS-7) were transfected with two plasmids: a test plasmid containing the gene for chloramphenicol acetyltransferase under the control of the thymidine kinase promoter and the insulin enhancer; and a competitor plasmid containing insulin enhancer sequences and the simian virus 40 origin of replication to permit its replication in the recipient cells. The presence of the competitor plasmid led to a 5- to 6-fold increase in chloramphenicol acetyltransferase activity as compared with the activity detected when insulin enhancer was absent from either the competitor or the test plasmid. A 5-fold increase in chloramphenicol acetyltransferase activity was also seen when the rat amylase enhancer was present on the competitor plasmid; in contrast the simian virus 40 enhancer exerted no effect. Efficient derepression required additional sequences downstream from those essential for enhancer activity. We propose that the activity of the rat insulin 1 enhancer is modulated by a negative trans-acting factor(s) that is active in cells not expressing insulin but is overridden by the dominant positive trans-acting factor(s) present in insulin-producing cells.
