DNA bending by nuclear receptors

Although steroid hormone receptors constitute an intensively studied family of ligand-regulated transcription factors, the mechanism by which these receptors activate transcription has not been defined. Evidence has accumulated from prokaryotic and eukaryotic systems that many transcription factors are capable of binding to their cognate recognition sequences and causing DNA to bend. Therefore, it has been hypothesized that DNA bending and transcription activation may be functionally coupled. We have utilized circular permutation analysis to examine the ability of the estrogen receptor DNA binding domain and the intact estrogen receptor to bend DNA fragments containing estrogen response elements (EREs). The DNA binding domain, which is a less potent activator of transcription, bent ERE containing DNA fragments less (34 degrees) than 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 when one ERE was present. These data suggest that DNA bending may play a role in transcription activation of estrogen responsive genes.