COORDINATED REGULATION OF AND TRANSCRIPTIONAL ACTIVATION BY XENOPUS THYROID-HORMONE AND RETINOID-X RECEPTORS

Thyroid hormone (T-3) plays a causative role in amphibian metamorphosi s, This regulation is thought to be mediated by heterodimers of T-3 re ceptors (TRs) and retinoid X receptors (RXRs). We report here that Xen opus TRs can indeed form strong heterodimers with Xenopus RXRs on the T-3 response element (TRE) present in Xenopus TRP beta genes. Using a T-3-responsive in vivo tran scription system established by introducin g TRs and RXRs into Xenopus oocytes, we demonstrated that TR-RXR heter odimers repressed TR beta gene promoter in the absence of T-3 and acti vated the promoter in the presence of the hormone. Furthermore, by ana lyzing the expression of TR and RXR genes, we showed that TR and RXR g enes were coordinately regulated in different tissues during metamorph osis. Thus high levels of their mRNAs are present in the limb during e arly stages of limb development when morphogenesis occurs and in the t ail toward the end of metamorphosis when it is being resorbed. Such co rrelations coupled with our TRE-binding and in vivo transcriptional ac tivation experiments provide strong evidence that TRs and RXRs functio n together to mediate the effects of T-3 during metamorphosis, These r esults further suggest a possible molecular basis for the temporal reg ulation of tissue-specific metamorphosis.