Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

SummarySkeletal 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 β-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.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (266 K)Download as PowerPoint slideHighlights► The transcription factor Nfix acts as a switch in skeletal muscle development ► Nfix activates fetal specific genes and represses embryonic genes ► Premature expression of Nfix activates fetal and suppresses embryonic genes ► Ablation of Nfix prevents fetal and maintains embryonic gene expression