A novel functional co-operation between MyoD, MEF2 and TR alpha 1 is sufficient for the induction of GLUT4 gene transcription

We report tripartite co-operation between MyoD, myocyte enhancer factor-2 ( MEF2) and the thyroid hormone receptor (TR alpha1) that takes place in the context of an 82-bp muscle-specific enhancer in the rat insulin-responsive glucose transporter (GLUT4) gene that is active in both cardiac and skeleta l muscle. In the L6E9 skeletal muscle cell line and in. 10T1/2 fibroblasts, a powerful synergistic activation of the GLUT4 enhancer relied on the over -expression of MyoD, MEF2 and TR alpha1 and the integrity of their respecti ve binding sites, and occurred when linked, to either a heterologous promot er or in the context of the native GLUT4, promoter. In cardiac myocytes, en hancer activity was dependent on the binding sites for MEF2 and TR alpha1. Furthermore, we show that in 10T1/2 fibroblasts, the forced expression of M yoD, MEF2 and TR alpha1 induced the expression of the endogenous, otherwise silent, GLUT4 gene. In all, our results indicate a novel functional co-ope ration between these three factors which is required for full activation of GLUT4 transcription. (C) 2001 Academic Press.