Nfix regulates fetal-specific transcription in developing skeletal muscle
Messina, Graziella × Biressi, Stefano Monteverde, Stefania Magli, Alessandro Cassano, Marco Perani, Laura Roncaglia, Elena Tagliafico, Enrico Starnes, Linda Campbell, Christine E Grossi, Milena Goldhamer, David J Gronostajski, Richard M Cossu, Giulio #
Cell vol:140 issue:4 pages:554-66
Skeletal myogenesis, like hematopoiesis, occurs in successive developmental stages that involve different cell populations and expression of different genes. We show here that the transcription factor nuclear factor one X (Nfix), whose expression is activated by Pax7 in fetal muscle, in turn activates the transcription of fetal specific genes such as MCK and beta-enolase while repressing embryonic genes such as slow myosin. In the case of the MCK promoter, Nfix forms a complex with PKC theta that binds, phosphorylates, and activates MEF2A. Premature expression of Nfix activates fetal and suppresses embryonic genes in embryonic muscle, whereas muscle-specific ablation of Nfix prevents fetal and maintains embryonic gene expression in the fetus. Therefore, Nfix acts as a transcriptional switch from embryonic to fetal myogenesis.