Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

Skeletal myogenesis, like hematopoiesis, occurs in successive developmental stages that involve dif- ferent cell populations and expression of different genes. We show here that the transcription factor nuclear factor one X (Nfix), whose expression is acti- vated by Pax7 in fetal muscle, in turn activates the transcription of fetal specific genes such as MCK and b-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. Pre- mature expression of Nfix activates fetal and sup- presses 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.