Figure 3. Mechanism of the dominant expression of RTH: In the absence of T3, occupancy of TRE by TR heterodimers (TR-TRAP) or dimers (TR-TR) suppresses transactivation through association with a corepressor (CoR). (A) T3-activated transcription mediated by TR-TRAP heterodimers involves the release of the CoR and association with coactivators (CoA) as well as (B) the removal of TR dimers from TRE releases their silencing effect and liberates TREs for the binding of active TR-TRAP heterodimers. The dominant negative effect of a mutant TR (mutTR), that does not bind T3, can be explained by the inhibitory effect of mutTR-containing-dimers and heterodimers that occupy TRE. Thus, T3 is unable to activate the mutTR-TRAP heterodimer (A’) or release TREs from the inactive mutTR homodimers (B’). [Modified from Refetoff et al. (5)].