GENOMIC ORGANIZATION OF THE RETINOIC ACID RECEPTOR GAMMA-GENE

The retinoic acid receptors (RAR) belong to the large family of ligand responsive gene regulatory proteins that includes receptors for steroid and thyroid hormones. These proteins contain two highly conserved domains, involved in determining their DNA and ligand binding activities. Three distinct RARs have been identified (RAR-alpha, beta, and gamma) which are encoded by genes on separate chromosomes. Additional isoforms of the three receptors have been described that all differ in the N-terminal regions. To gain insight into the genomic organization and mechanisms of RAR isoform generation, we have analyzed the genomic structure of the RAR-gamma gene. The major portion of the RAR-gamma protein, including DNA and ligand binding domains, is encoded by seven exons that are identical for all RARg isoforms and are represented by a relatively small portion of the RAR-gamma gene. The major portion of this gene encodes separate N-terminal exons for gamma-1 and gamma-2 isoforms and several exons for gamma-1 untranslated regions. We show that RAR-gamma-2 transcription is regulated by its own promoter. In comparison with the steroid receptor subfamily, various splice sites of RAR-gamma occur at altered positions, suggesting that the RAR subfamily has diverged early during evolution.