Trapping and characterization of novel retinoid response elements

Retinoids, such as retinoic acid (RA), play a critical role in normal vertebrate development and physiology. However, embryonic exposure to excess retinoids also causes severe malformations. Retinoids bind RA receptors and retinoid X receptors, thus activating a plethora of genes. Separating the genes induced directly by retinoid-bound receptors from those induced subsequently by other transcription factors is difficult. The loose consensus defining known RA responsive elements (RAREs) further complicates this effort. We developed a yeast-based system to trap functional RAREs in the mouse genome. Several of the clones contain RAREs near RA-induced genes. Mammalian reporter gene analyses and EMSAs showed that these are bona fide RAREs. This functional genomics approach should identify RA-regulated genes that initiate critical signaling cascades in cells.