Cordle S R, Whelan J, Henderson E, Masuoka H, Weil P A, Stein R
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Mol Cell Biol. 1991 May;11(5):2881-6. doi: 10.1128/mcb.11.5.2881-2886.1991.
Selective transcription of the insulin gene in pancreatic beta cells is regulated by its enhancer, located between nucleotides -340 and -91 relative to the transcription start site. Transcription from the enhancer is controlled by both positive- and negative-acting cellular factors. Cell-type-specific expression is mediated principally by a single cis-acting enhancer element located between -100 and -91 in the rat insulin II gene (referred to as the insulin control element [ICE]), which is acted upon by both of these cellular activities. Analysis of the effect of 5' deletions within the insulin enhancer has identified a region between nucleotides -217 and -197 that is also a site of negative control. Deletion of these sequences from the 5' end of the enhancer leads to transcription of the enhancer in non-insulin-producing cells, even though the ICE is intact. Derepression of this ICE-mediated effect was shown to be due to the binding of a ubiquitously distributed cellular factor to a sequence element which resides just upstream of the ICE (i.e., between nucleotides -110 and -100). We discuss the possible relationship of these results to cell-type-specific regulation of the insulin gene.
胰岛素基因在胰腺β细胞中的选择性转录受其增强子调控，该增强子位于相对于转录起始位点的核苷酸-340至-91之间。增强子的转录受正性和负性作用的细胞因子共同控制。细胞类型特异性表达主要由大鼠胰岛素II基因中位于-100至-91之间的单个顺式作用增强子元件介导（称为胰岛素控制元件[ICE]），这两种细胞活性均作用于该元件。对胰岛素增强子内5'缺失效应的分析确定了核苷酸-217至-197之间的一个区域也是负调控位点。从增强子的5'端删除这些序列会导致增强子在非胰岛素产生细胞中发生转录，即使ICE完整。这种ICE介导效应的去抑制被证明是由于一种广泛分布的细胞因子与位于ICE上游（即核苷酸-110至-100之间）的一个序列元件结合所致。我们讨论了这些结果与胰岛素基因细胞类型特异性调控的可能关系。
