|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.
|Source:||Cell Reports 17: 2354-2366 (Journal)|
|Registered Authors:||Beltrame, Monica|
|Keywords:||MyHC-I, Nfix, Sox6, myogenesis|
|PubMed:||27880909 Full text @ Cell Rep.|
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.
ABSTRACTSox6 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.