title: Nfix regulates fetal-specific transcription in developing skeletal muscle.
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.
authors.affiliation: San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Graziella
authors.initials: G
authors.lastname: Messina
authors.forename: Stefano
authors.initials: S
authors.lastname: Biressi
authors.forename: Stefania
authors.initials: S
authors.lastname: Monteverde
authors.forename: Alessandro
authors.initials: A
authors.lastname: Magli
authors.forename: Marco
authors.initials: M
authors.lastname: Cassano
authors.forename: Laura
authors.initials: L
authors.lastname: Perani
authors.forename: Elena
authors.initials: E
authors.lastname: Roncaglia
authors.forename: Enrico
authors.initials: E
authors.lastname: Tagliafico
authors.forename: Linda
authors.initials: L
authors.lastname: Starnes
authors.forename: Christine E
authors.initials: CE
authors.lastname: Campbell
authors.forename: Milena
authors.initials: M
authors.lastname: Grossi
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldhamer
authors.forename: Richard M
authors.initials: RM
authors.lastname: Gronostajski
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
mesh_terms: D000818:Animals; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D064326:MEF2 Transcription Factors; D051379:Mice; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000196:embryology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D051839:NFI Transcription Factors / Q000378:metabolism*; D051763:PAX7 Transcription Factor / Q000378:metabolism; D010751:Phosphopyruvate Hydratase; D011493:Protein Kinase C / Q000378:metabolism; D000074121:Protein Kinase C-theta; D014158:Transcription, Genetic
chemical_list: D007527:Isoenzymes; D064326:MEF2 Transcription Factors; C578036:Mef2a protein, mouse; D018006:Myogenic Regulatory Factors; D050778:NFATC Transcription Factors; D051839:NFI Transcription Factors; C467907:Nfatc4 protein, mouse; C497650:Nfix protein, mouse; D051763:PAX7 Transcription Factor; C497322:Pax7 protein, mouse; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D010751:Phosphopyruvate Hydratase