Author:

Keywords:

Animals, Fetus, Gene Expression Regulation, Developmental, Humans, Isoenzymes, Mice, Muscle Development, Muscle, Skeletal, Myogenic Regulatory Factors, NFATC Transcription Factors, NFI Transcription Factors, PAX7 Transcription Factor, Phosphopyruvate Hydratase, Protein Kinase C, Transcription, Genetic, Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, NUCLEAR-FACTOR-I, GENE-EXPRESSION, BETA-GLOBIN, ENHANCER, BINDING, PROTEIN, PROGENITORS, DOWNSTREAM, INTERACTS, MYOBLASTS, MEF2 Transcription Factors, Protein Kinase C-theta, 06 Biological Sciences, 11 Medical and Health Sciences, Developmental Biology, 31 Biological sciences, 32 Biomedical and clinical sciences

Abstract:

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.