Walters M C, Fiering S, Eidemiller J, Magis W, Groudine M, Martin D I
Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7125-9. doi: 10.1073/pnas.92.15.7125.
We have studied enhancer function in transient and stable expression assays in mammalian cells by using systems that distinguish expressing from nonexpressing cells. When expression is studied in this way, enhancers are found to increase the probability of a construct being active but not the level of expression per template. In stably integrated constructs, large differences in expression level are observed but these are not related to the presence of an enhancer. Together with earlier studies, these results suggest that enhancers act to affect a binary (on/off) switch in transcriptional activity. Although this idea challenges the widely accepted model of enhancer activity, it is consistent with much, if not all, experimental evidence on this subject. We hypothesize that enhancers act to increase the probability of forming a stably active template. When randomly integrated into the genome, enhancers may affect a metastable state of repression/activity, permitting expression in regions that would not permit activity of an isolated promoter.
我们通过使用能够区分表达细胞和非表达细胞的系统，在哺乳动物细胞的瞬时和稳定表达测定中研究了增强子功能。当以这种方式研究表达时，发现增强子会增加构建体激活的概率，但不会增加每个模板的表达水平。在稳定整合的构建体中，观察到表达水平存在很大差异，但这些差异与增强子的存在无关。与早期研究一起，这些结果表明增强子作用于影响转录活性中的二元（开/关）开关。尽管这个想法挑战了广泛接受的增强子活性模型，但它与关于这个主题的很多（如果不是全部）实验证据是一致的。我们假设增强子作用于增加形成稳定活性模板的概率。当随机整合到基因组中时，增强子可能会影响抑制/活性的亚稳态，从而允许在不允许孤立启动子活性的区域中表达。
