PUBLICATION
Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle
- Authors
- Taglietti, V., Maroli, G., Cermenati, S., Monteverde, S., Ferrante, A., Rossi, G., Cossu, G., Beltrame, M., Messina, G.
- ID
- ZDB-PUB-161124-2
- 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.
Citation
Taglietti, V., Maroli, G., Cermenati, S., Monteverde, S., Ferrante, A., Rossi, G., Cossu, G., Beltrame, M., Messina, G. (2016) Nfix Induces a Switch in Sox6 Transcriptional Activity to Regulate MyHC-I Expression in Fetal Muscle. Cell Reports. 17:2354-2366.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping