Switching of DNA secondary structure in proenkephalin transcriptional regulation

Proper transcriptional regulation of the proenkephalin gene requires a switch between distinct factor binding sites that cannot exist at the same time. Each of the sites is formed from a nearly palindromic region that contains two functionally defined cAMP response elements. The region can switch between cruciform and linear duplex. Formation of the cruciform creates an alternative binding site for mediators of second messenger-directed transcription and abolishes the site present in the native duplex form. Use of the cruciform site has been shown to correlate with activated transcription. Analysis of DNA structure, protein binding, and gene expression from plasmids with mutant enhancers shows, however, that both sites are required for regulation of transcription. The two distinct structures form within the same enhancer. Shifting the balance between the two alters transcriptional response.