Résumé
The BTG1 gene was isolated from a translocation break point in a case of B-cell Chronic Lymphocytic Leukaemia. Its product belongs to an antiproliferative family of proteins. Previous work from our laboratory have established that T3 indirectly induces BTG1 expression at cell confluence and stimulates its nuclear localization in avian myoblasts. Furthermore, BTG1 overexpression mimics the positive myogenic influence of T3 by inducing myoblast withdrawal from the cell cycle and stimulating terminal differentiation. In this study, we searched for the molecular mechanisms involved in BTG1 myogenic influence in vitro. We found that BTG1 is a new coactivator of transcription factors that regulates positively myoblast differentiation : T3 nuclear receptor (c ErbA a1), RAR, myogenic factors MyoD, Myogenin, Myf5, and c Jun. After characterization of the domains allowing the interactions between BTG1 and MyoD or c ErbA a1, we established that deletion of these domains severely impairs BTG1 myogenic influence, demonstrating that its myogenic activity and its coactivator function are directly related. As we have previously shown that BTG1 expression is induced at the onset of myoblast differentiation, it appears that this coactivator could exert a key role in myoblasts proliferation/differentiation transition, by inducing stimulation of the expression of targets genes of nuclear receptors and myogenic factors. In the second part of this study, we observed that MyoD interacts physically with c-ErbA a1, thus satisfactorily explaining the functional interactions between these two factors previously described by our team. In addition, we demonstrated the occurrence of a competition between CMD1 and c-ErbA a1 for BTG1 recruitment. Finally, we have characterized the expression pattern of BTG1 in vivo during chicken embryogenesis. We found that BTG1 is precociously expressed in the somites and limb buds, suggesting that BTG1 is involved in muscle formation in vivo