NEW RETINOID-X RECEPTOR SUBTYPES IN ZEBRA FISH (DANIO-RERIO) DIFFERENTIALLY MODULATE TRANSCRIPTION AND DO NOT BIND 9-CIS RETINOIC ACID

Retinoid X receptors (RXRs), along with retinoic acid (RA) receptors ( RARs), mediate the effects of RA on gene expression. Three subtypes of RXRs (alpha, beta, and gamma) which bind to and are activated by the 9-cis stereoisomer of RA have been characterized. They activate gene t ranscription by binding to specific sites on DNA as homodimers or as h eterodimers with RARs and other related nuclear receptors, including t he vitamin D receptor, thyroid hormone receptors (TRs), and peroxisome proliferator-activated receptors. Two additional RXR subtypes (delta and epsilon) isolated from zebra fish cDNA libraries are described her e; although both subtypes form DNA-binding heterodimers with RARs and TR, neither binds 9-cis RA, and both are transcriptionally inactive on RXR response elements. In cotransfection studies with TR, the delta s ubtype was found to function in a dominant negative manner, while the epsilon subtype had a slight stimulatory effect on thyroid hormone (T3 )-dependent transcriptional activity. The discovery of these two novel receptors in zebra fish expands the functional repertoire of RXRs to. include ligand-independent and dominant negative modulation of type I I receptor function.