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
-
- Conserved Sequence
- Myosin Heavy Chains/metabolism*
- Embryo, Nonmammalian/metabolism
- Zebrafish Proteins/metabolism*
- MEF2 Transcription Factors/metabolism
- PubMed
- 27880909 Full text @ Cell Rep.
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.
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