Avian MyoD and c-Jun Coordinately Induce Transcriptional Activity of the 3,5,3′-Triiodothyronine Nuclear Receptor c-ErbAα1 in Proliferating Myoblasts

Although physical interactions with other receptors have been reported, heterodimeric complexes of T3 nuclear receptors (TR) with retinoid X receptors (RXRs) are considered as major regulators of T3 target gene expression. However, despite the potent T3 influence in proliferating myoblasts, RXR isoforms are not expressed during proliferation, raising the question of the nature of the complex involved in TRα transcriptional activity. We have previously established that c-Jun induces TRα1 transcriptional activity in proliferating myoblasts not expressing RXR. This regulation is specific to the muscle lineage, suggesting the involvement of a muscle-specific factor. In this study, we found that MyoD expression in HeLa cells stimulates TRα1 activity, an influence potentiated by c-Jun coexpression. Similarly, in the absence of RXR, MyoD or c-Jun overexpression in myoblasts induces TRα1 transcriptional activity through a direct repeat 4 or an inverted palindrome 6 thyroid hormone response element. The highest rate of activity was recorded when c-Jun and MyoD were coexpressed. Using c-Jun-negative dominants, we established that MyoD influence on TRα1 activity needs c-Jun functionality. Furthermore, we demonstrated that TRα1 and MyoD physically interact in the hinge region of the receptor and the transactivation and basic helix loop helix domains of MyoD. RXR expression (spontaneously occurring at the onset of myoblast differentiation) in proliferating myoblasts abrogates these interactions. These data suggest that in the absence of RXR, TRα1 transcriptional activity in myoblasts is mediated through a complex including MyoD and c-Jun.