The over-expression of the transcription factor BERF-1/ZBP-89/Zfp148 induces the loss of the myogenic potential in murine C2.7 and C3H-MyoD cells

We have previously demonstrated that the ectopic abnormal expression of the transcription factor BERF- 1/ZBP-89/Zfp148 in C2.7 myoblasts results in the inhibition of the myogenic differentiation program through the down-regulation of the myogenic regulatory factor MyoD. Stable myoblast clones over-expressing the factor are unable to fuse and form myotubes in vitro. The transgene expression induces a wide pattern of alterations both at cellular and molecular level when compared to wild type cells, as demonstrated by the analysis of mRNAs and proteins which showed the altered expression of genes involved in myogenic differentiation, cell growth and cell cycle regulation. This prompted us to verify if the effect of the overexpression of BERF-1/ZBP-89/Zfp148 on the myogenic program is independent from the cellular background. For this purpose we used the C3H-MyoD fibroblasts that are able to differentiate into myotubes due to the forced expression of the myogenic regulatory factor. The over-expression of BERF-1/ZBP-89/Zfp148 in C3H-MyoD induced the down-regulation of MyoD expression and the loss of myogenic potential. Our data demonstrate that BERF-1/ZBP-89/Zfp148 inhibits the myogenic differentiation independently from the cellular context and support its potential role as a coregulator for the correct expression pattern of genes involved in the execution of the myogenic program.