Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle
| Autor: | Valentina, Taglietti, Giovanni, Maroli, Solei, Cermenati, Stefania, Monteverde, Andrea, Ferrante, Giuliana, Rossi, Giulio, Cossu, Monica, Beltrame, Graziella, Messina |
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| Rok vydání: | 2015 |
| Předmět: |
Embryo
Nonmammalian Transcription Genetic macromolecular substances MyHC-I Muscle Development Models Biological Article Evolution Molecular Myoblasts Mice Fetus Animals Muscle Skeletal Promoter Regions Genetic Conserved Sequence Zebrafish Myosin Heavy Chains MEF2 Transcription Factors Nfix Gene Expression Regulation Developmental Zebrafish Proteins musculoskeletal system NFI Transcription Factors Phenotype Sox6 myogenesis tissues SOXD Transcription Factors Protein Binding |
| Zdroj: | Cell Reports |
| ISSN: | 2211-1247 |
| Popis: | Summary 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. Graphical Abstract Highlights • Sox6 has opposite roles in MyHC-I regulation during embryonic and fetal myogenesis • In embryonic muscle, Sox6 enhances MyHC-I expression via regulation of Mef2C • In fetal muscle, Nfix is required for Sox6-mediated repression of MyHC-I • The Sox6 and Nfixa orthologs cooperate in repressing smyhc1 in zebrafish Taglietti et al. reveal molecular mechanisms defining muscle fiber specification, driven by the key transcription factors Nfix and Sox6, during mouse and zebrafish development. They show that Nfix reverses Sox6 function between embryonic and fetal phases of myogenesis, allowing the proper expression of slow MyHC. |
| Databáze: | OpenAIRE |
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