Enhancers increase the probability but not the level of gene expression - PubMed (original) (raw)
Enhancers increase the probability but not the level of gene expression
M C Walters et al. Proc Natl Acad Sci U S A. 1995.
Abstract
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.
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References
- Biochemistry. 1979 Dec 11;18(25):5726-31 - PubMed
- J Exp Med. 1994 Oct 1;180(4):1251-62 - PubMed
- Nucleic Acids Res. 1981 Nov 25;9(22):6047-68 - PubMed
- Cell. 1981 Dec;27(2 Pt 1):299-308 - PubMed
- J Mol Biol. 1982 Apr 15;156(3):549-65 - PubMed
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