An enhancer stimulates transcription in trans when attached to the promoter via a protein bridge

Two principal models have been invoked to explain transcriptional stimulation of RNA polymerase II genes by enhancers/upstream promoter elements: in one, upstream regulatory sequences directly interact with proximal promoter elements via proteins bound to the DNA ("looping" model); in the other, RNA polymerase II (or a transcription factor) binds to distal sequences and then scans along the DNA until it reaches the promoter ("scanning" or "entry site" model). So far, it has been reported that enhancers or upstream promoter elements transmit their effect on a gene only via covalently closed DNA, i.e., in a cis configuration. The looping model predicts, however, that the effect can be transmitted also in certain trans configurations. Here we demonstrate that an enhancer from SV40 or cytomegalovirus can stimulate transcription in vitro even when noncovalently attached to the beta-globin promoter via the proteins streptavidin or avidin. These findings are consistent with the looping model rather than the scanning model. In addition, stimulation of transcription in trans, as shown by our experiments, may be found in nature in phenomena such as transvection, where one chromosome affects gene expression in the paired homolog.