To be or not to be active: the stochastic nature of enhancer action

Transcriptional enhancers are traditionally considered to regulate the rate at which a linked promoter transcribes mRNA, but recent experiments suggest a reevaluation of this model is necessary. Single-cell assays of transgenes reveal that enhancers increase the probability that a reporter gene will be active, but have little or no effect on the transcription rate once a gene has been activated. These results raise the question of how enhancers affect gene expression in their native contexts. A simple interpretation is that enhancers act in a stochastic fashion to increase the probability that a regulated gene will be transcribed; such a model is compatible with programs of cell differentiation in which multiple similar cells subject to similar environmental stimuli do not respond uniformly. BioEssays 22:381–387, 2000. © 2000 John Wiley & Sons, Inc.