Avian MyoD and c-Jun coordinately induce transcriptional activity of the 3,5,3'-triiodothyronine nuclear receptor c-ErbAalpha1 in proliferating myoblasts.
Although physical interactions with other receptors have been reported, heterodimeric complexes of T(3) nuclear receptors (TR) with retinoid X receptors (RXRs) are considered as major regulators of T(3) target gene expression. However, despite the potent T(3) influence in proliferating myoblasts, RXR isoforms are not expressed during proliferation, raising the question of the nature of the complex involved in TRalpha transcriptional activity. We have previously established that c-Jun induces TRalpha1 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 TRalpha1 activity, an influence potentiated by c-Jun coexpression. Similarly, in the absence of RXR, MyoD or c-Jun overexpression in myoblasts induces TRalpha1 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 TRalpha1 activity needs c-Jun functionality. Furthermore, we demonstrated that TRalpha1 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, TRalpha1 transcriptional activity in myoblasts is mediated through a complex including MyoD and c-Jun.
Unité d'Endocrinologie Cellulaire, Unité Mixte de Recherche Différenciation Cellulaire et Croissance, Institut National de la Recherche Agronomique, 2 place Viala, 34060 Montpellier Cedex 1, France.
Muriel
M
Busson
Laetitia
L
Daury
Pascal
P
Seyer
Stéphanie
S
Grandemange
Laurence
L
Pessemesse
François
F
Casas
Chantal
C
Wrutniak-Cabello
Gérard
G
Cabello
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D049109:Cell Proliferation; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D017570:MyoD Protein / Q000378:metabolism / Q000502:physiology*; D032446:Myoblasts / Q000166:cytology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism / Q000502:physiology*; D011784:Quail; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D037021:Thyroid Hormone Receptors alpha / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014285:Triiodothyronine, Reverse / Q000378:metabolism*
D017570:MyoD Protein; D016755:Proto-Oncogene Proteins c-jun; D011988:Receptors, Thyroid Hormone; D047490:Retinoid X Receptor alpha; D037021:Thyroid Hormone Receptors alpha; D014285:Triiodothyronine, Reverse