SWITCHING OF DNA SECONDARY STRUCTURE IN PROENKEPHALIN TRANSCRIPTIONALREGULATION

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 regi on that contains two functionally defined cAMP response elements. The region can switch between cruciform and linear duplex. Formation of th e cruciform creates an alternative binding site for mediators of secon d messenger-directed transcription and abolishes the site present in t he native duplex form. Use of the cruciform site has been shown to cor relate with activated transcription. Analysis of DNA structure, protei n binding, and gene expression from plasmids with mutant enhancers sho ws, however, that both sites are required for regulation of transcript ion. The two distinct structures form within the same enhancer. Shifti ng the balance between the two alters transcriptional response.