Nfix regulates fetal-specific transcription in developing skeletal muscle.
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.
Messina
Graziella
G
San Raffaele Scientific Institute, Milan, Italy.
Biressi
Stefano
S
Monteverde
Stefania
S
Magli
Alessandro
A
Cassano
Marco
M
Perani
Laura
L
Roncaglia
Elena
E
Tagliafico
Enrico
E
Starnes
Linda
L
Campbell
Christine E
CE
Grossi
Milena
M
Goldhamer
David J
DJ
Gronostajski
Richard M
RM
Cossu
Giulio
G
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
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