ZFIN ID: ZDB-PUB-161124-2
Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle
Taglietti, V., Maroli, G., Cermenati, S., Monteverde, S., Ferrante, A., Rossi, G., Cossu, G., Beltrame, M., Messina, G.
Date: 2016
Source: Cell Reports   17: 2354-2366 (Journal)
Registered Authors: Beltrame, Monica
Keywords: MyHC-I, Nfix, Sox6, myogenesis
MeSH Terms:
  • Animals
  • Conserved Sequence
  • Embryo, Nonmammalian/metabolism
  • Evolution, Molecular
  • Fetus/embryology*
  • Fetus/metabolism
  • Gene Expression Regulation, Developmental
  • MEF2 Transcription Factors/metabolism
  • Mice
  • Models, Biological
  • Muscle Development/genetics
  • Muscle, Skeletal/embryology*
  • Muscle, Skeletal/metabolism
  • Myoblasts/metabolism
  • Myosin Heavy Chains/metabolism*
  • NFI Transcription Factors/metabolism*
  • Phenotype
  • Promoter Regions, Genetic
  • Protein Binding/genetics
  • SOXD Transcription Factors/genetics*
  • Transcription, Genetic*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 27880909 Full text @ Cell Rep.
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.