DNA BENDING BY NUCLEAR RECEPTORS

Although steroid hormone receptors constitute an intensively studied f amily of ligand-regulated transcription factors, the mechanism by whic h these receptors activate transcription has not been defined. Evidenc e has accumulated from prokaryotic and eukaryotic systems that many tr anscription factors are capable of binding to their cognate recognitio n sequences and causing DNA to bend. Therefore, it has been hypothesiz ed that DNA bending and transcription activation maybe functionally co upled. We have utilized circular permutation analysis to examine the a bility of the estrogen receptor DNA binding domain and the intact estr ogen receptor to bend DNA fragments containing estrogen response eleme nts (EREs). The DNA binding domain, which is a less potent activator o f transcription, bent ERE containing DNA fragments less (34 degrees) t han the intact estrogen receptor (56 degrees), which is a more potent activator of transcription. In addition, when two EREs were present in a DNA fragment, the degree of DNA bending observed was greater than w hen one ERE was present. These data suggest that DNA bending may play a role in transcription activation of estrogen responsive genes.