Three principal models have been proposed for positive regulation from distant (enhancer) sites. In the first, the regulatory protein (or RNA polymerase) associates with the DNA at the enhancer site and then traverses the DNA to the promoter site (scanning model). In the second, the enhancer binding protein initiates a change in DNA structure that propagated from the enhancer to the promoter, thereby activating transcription (structural transmission model). In the third, the enhancer bound regulatory protein activates transcription by a direct protein-protein interaction with RNA polymerase at the promoter (DNA-looping or nucleoprotein model). DNA-looping is currently favored as the most likely mechanism for distant regulatory interactions.