The triiodothyronine nuclear receptor c-ErbAalpha1 inhibits avian MyoD transcriptional activity in myoblasts.
Thyroid hormone stimulates myoblast differentiation, through an inhibition of AP-1 activity occurring at the onset of differentiation. In this study we found that the T3 nuclear receptor c-ErbAalpha1 (T3Ralpha1) is involved in a mechanism preserving the duration of myoblast proliferation. Independently of the hormone presence, T3Ralpha1 represses avian MyoD transcriptional activity. Using several mutants of T3Ralpha1, we found that the hinge region plays a crucial role in the inhibition of MyoD activity. In particular, mutations of two small basic sequences included in alpha helices abrogate the T3Ralpha1/MyoD functional interaction. Similarly, the T3 receptor also represses myogenin transcriptional activity. Therefore, despite stimulating avian myoblast differentiation by a T3-dependent pathway not involving myogenic factors, T3Ralpha1 contributes to maintain an optimal myoblast proliferation period by inhibiting MyoD and myogenin activity.
Daury
L
L
Unité d'Endocrinologie Cellulaire, UMR Différenciation Cellulaire et Croissance (INRA, Université Montpellier II, ENSAM), Institut National de la Recherche Agronomique (INRA), 2 place Viala, 34060 Montpellier Cedex 1, France.
Busson
M
M
Casas
F
F
Cassar-Malek
I
I
Wrutniak-Cabello
C
C
Cabello
G
G
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D005786:Gene Expression Regulation; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D017570:MyoD Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018008:Myogenin / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011784:Quail; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology
D017570:MyoD Protein; C503801:Myog protein, mouse; C503803:Myog protein, rat; D018008:Myogenin; D011988:Receptors, Thyroid Hormone; D012097:Repressor Proteins; D014284:Triiodothyronine