title: Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle.
abstract: Sox6 belongs to the Sox gene family and plays a pivotal role in fiber type differentiation, suppressing transcription of slow-fiber-specific genes during fetal development. Here, we show that Sox6 plays opposite roles in MyHC-I regulation, acting as a positive and negative regulator of MyHC-I expression during embryonic and fetal myogenesis, respectively. During embryonic myogenesis, Sox6 positively regulates MyHC-I via transcriptional activation of Mef2C, whereas during fetal myogenesis, Sox6 requires and cooperates with the transcription factor Nfix in repressing MyHC-I expression. Mechanistically, Nfix is necessary for Sox6 binding to the MyHC-I promoter and thus for Sox6 repressive function, revealing a key role for Nfix in driving Sox6 activity. This feature is evolutionarily conserved, since the orthologs Nfixa and Sox6 contribute to repression of the slow-twitch phenotype in zebrafish embryos. These data demonstrate functional cooperation between Sox6 and Nfix in regulating MyHC-I expression during prenatal muscle development.
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Taglietti
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Maroli
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Solei
authors.initials: S
authors.lastname: Cermenati
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Monteverde
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ferrante
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy; Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Oxford Road, M13 9PL Manchester, UK.
authors.forename: Giulio
authors.initials: G
authors.lastname: Cossu
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Beltrame
authors.affiliation: Department of Biosciences, University of Milan, Milan 20133, Italy. Electronic address: graziella.messina@unimi.it.
authors.forename: Graziella
authors.initials: G
authors.lastname: Messina
mesh_terms: D000818:Animals; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000378:metabolism; D019143:Evolution, Molecular; D005333:Fetus / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D064326:MEF2 Transcription Factors / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D032446:Myoblasts / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism*; D051839:NFI Transcription Factors / Q000378:metabolism*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D055755:SOXD Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D064326:MEF2 Transcription Factors; D051839:NFI Transcription Factors; C497650:Nfix protein, mouse; D055755:SOXD Transcription Factors; D029961:Zebrafish Proteins; C581026:nfixa protein, zebrafish; D018995:Myosin Heavy Chains
keywords: MyHC-I; Nfix; Sox6; myogenesis