Cell Reports
Volume 17, Issue 9, 22 November 2016, Pages 2354-2366
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Article
Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle

https://doi.org/10.1016/j.celrep.2016.10.082Get rights and content
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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

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.

Keywords

Sox6
Nfix
MyHC-I
myogenesis

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Co-first author

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Present address: Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany

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Lead Contact