Reconstitution of retinoid X receptor function and combinatorial regulation of other nuclear hormone receptors in the yeast Saccharomyces cerevisiae

The nuclear hormone receptor family of transcription factors regulates gene expression via a complex combinatorial network of interactions. Of particular interest is the ability of retinoid X receptors (RXRs) to form heterodimers with retinoic acid receptors (RARs) and thyroid hormone receptors (TRs), thereby modifying their activities. We report here that RXR, RAR, and TR function can be reconstituted in the yeast Saccharomyces cerevisiae and demonstrate that the combinatorial regulation seen in vertebrate cells can be reproduced in the yeast background. Using this system, we have shown that RARs respond to a wide variety of retinoid ligands but that RXRs are specific for the 9-cis isomer of retinoic acid. RXR enhanced the activity of RARs and TRs on a variety of hormone response elements without demonstrably altering their DNA specificity. Interestingly, the ability of RXR to potentiate gene activation by RARs and by TRs varied for different receptor isoforms.