c-Myb inhibits myogenic differentiation through repression of MyoD

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 es...

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Bibliographic Details
Published inExperimental cell research Vol. 309; no. 2; pp. 419 - 428
Main Authors Kaspar, Petr, Pajer, Petr, Sedlak, David, Tamaoki, Taiki, Dvorak, Michal
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.10.2005
Elsevier BV
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Summary: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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ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2005.06.016