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Publication : c-Myb inhibits myogenic differentiation through repression of MyoD.

First Author  Kaspar P Year  2005
Journal  Exp Cell Res Volume  309
Issue  2 Pages  419-28
PubMed ID  16055116 Mgi Jnum  J:102555
Mgi Id  MGI:3607754 Doi  10.1016/j.yexcr.2005.06.016
Citation  Kaspar P, et al. (2005) c-Myb inhibits myogenic differentiation through repression of MyoD. Exp Cell Res 309(2):419-28
abstractText  c-Myb, known to play a central role in hematopoiesis, is also an important factor involved in myogenesis. Here, we found that the c-myb gene is expressed in proliferating C2C12 myoblasts and turned off in differentiating cells. Detailed analysis of c-myb RNAs revealed that the cell density is the essential factor determining c-myb expression. Both c-myb and its alternatively spliced form c-mybE9A RNAs are down-regulated in confluent cells. Constitutive expression of exogenous c-myb in C2C12 cells inhibits their terminal differentiation. It is shown that the c-Myb protein physically interacts with MyoD, the key regulator of myogenesis, and inhibits MyoD-dependent transcription. The interaction domains are the DNA binding domain of c-Myb and the bHLH motif of MyoD. Our data suggest that in proliferating cells c-Myb binds MyoD and inhibits its transcriptional activity until cell-cell contacts are established and c-myb expression is switched off. Thus, the c-Myb protein may be one of factors ensuring that proliferating myoblasts remain undifferentiated.
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