title: Enhancers increase the probability but not the level of gene expression.
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.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle 98104, USA.
authors.forename: M C
authors.initials: MC
authors.lastname: Walters
authors.forename: S
authors.initials: S
authors.lastname: Fiering
authors.forename: J
authors.initials: J
authors.lastname: Eidemiller
authors.forename: W
authors.initials: W
authors.lastname: Magis
authors.forename: M
authors.initials: M
authors.lastname: Groudine
authors.forename: D I
authors.initials: DI
authors.lastname: Martin
mesh_terms: D015139:Blotting, Southern; D002843:Chromatin / Q000648:ultrastructure; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D005434:Flow Cytometry; D018628:Gene Dosage; D015870:Gene Expression; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008957:Models, Genetic; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D002843:Chromatin