DNA BENDING BY RETINOID-X RECEPTOR-CONTAINING RETINOID AND THYROID-HORMONE RECEPTOR COMPLEXES

Retinoid X receptors (RXR) have been identified as common subunits in the regulation of multiple hormonal signaling pathways. Using circular permutation and phasing analysis of specific response elements, we pr esent evidence that RXR-retinoic acid receptor and RXR-thyroid hormone receptor heterodimer or RXR-RXR homodimer complexes induce directed D NA bends when bound to their cognate response elements. The extent of DNA bending induced by the RXRalpha-containing complexes varied and de pended on the structure of the DNA-binding sites and the RXR partners. The overall bending orientation for RXR-containing complexes is direc ted toward the major groove of the DNA helix at the center of hormone response elements. Our observation implicates DNA bending as a possibl e mechanism underlying transcriptional regulation of distinct retinoid and thyroid hormone responsive genes.