Abstract
Thyroid hormone (T3) plays a causative role in amphibian metamorphosis. This regulation is thought to be mediated by heterodimers of T3 receptors (TRs) and retinoid X receptors (RXRs). We report here that Xenopus TRs can indeed form strong heterodimers with Xenopus RXRs on the T3 response element (TRE) present in Xenopus TR beta genes. Using a T3-responsive in vivo transcription system established by introducing TRs and RXRs into Xenopus oocytes, we demonstrated that TR-RXR heterodimers repressed TR beta gene promoter in the absence of T3 and activated the promoter in the presence of the hormone. Furthermore, by analyzing the expression of TR and RXR genes, we showed that TR and RXR genes were coordinately regulated in different tissues during metamorphosis. Thus high levels of their mRNAs are present in the limb during early stages of limb development when morphogenesis occurs and in the tail toward the end of metamorphosis when it is being resorbed. Such correlations coupled with our TRE-binding and in vivo transcriptional activation experiments provide strong evidence that TRs and RXRs function together to mediate the effects of T3 during metamorphosis. These results further suggest a possible molecular basis for the temporal regulation of tissue-specific metamorphosis.
Highlights
Thyroid hormone (T3) plays a causative role in amphibian metamorphosis
Our current work clearly demonstrate that both TR a and TRf3can form st rong Ta response element (TRE)-binding het erodimers with either RXRa or RXRy
The TRE sequence preference is identical among different heterodimers a nd is the same as observed in mammals and bird s, i.e. the dir ect repeats of AGGTCA separated by 4 base pairs being th e stronger TRE than either two inverted re peat of AGGTCA (TREp) or TREgh
Summary
Thyroid hormone (T3) plays a causative role in amphibian metamorphosis. This regulation is thought to be mediated by heterodimers ofTa receptors (TRs) and retinoid X receptors (RXRs). High levels of their mRNAs are present in the limb during early stages of limb development when morphogenesis occurs and in the tail toward the end of metamorphosis when it is being resorbed Such correlations coupled with our TRE-binding and in vivo transcriptional activation experiments provide strong evidence that TRs and RXRs function together to mediate the effects of Ta during metamorphosis. The heterodimers between TRs and RXRs confer specificity for gene regulation by thyroid hormone in cotransfection experiments in tissue culture cells It remains to be determined whether TRRXR heterodimers are the active complexes mediating the effect of thyroid hormone in vivo. We show that Xenopus TR-RXR heterodimers can bind to the TRE present in Xenopus TRJ3 genes with high specificity and affinity and activate the TRJ3promoter in a hormone-dependent manner
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