Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle

Graziella Messina, Stefano Biressi, Stefania Monteverde, Alessandro Magli, Marco Cassano, Laura Perani, Elena Roncaglia, Enrico Tagliafico, Linda Starnes, Christine E. Campbell, Milena Grossi, David J. Goldhamer, Richard M. Gronostajski, Giulio Cossu

Research output: Contribution to journalArticle

110 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)554-566
Number of pages13
JournalCell
Volume140
Issue number4
DOIs
StatePublished - Feb 19 2010

Keywords

  • DEVBIO

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    Messina, G., Biressi, S., Monteverde, S., Magli, A., Cassano, M., Perani, L., Roncaglia, E., Tagliafico, E., Starnes, L., Campbell, C. E., Grossi, M., Goldhamer, D. J., Gronostajski, R. M., & Cossu, G. (2010). Nfix Regulates Fetal-Specific Transcription in Developing Skeletal Muscle. Cell, 140(4), 554-566. https://doi.org/10.1016/j.cell.2010.01.027