Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2036552 | Cell | 2010 | 13 Pages |
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