c-Myb inhibits myogenic differentiation through repression of MyoD

Journal Article · Sat Oct 01 04:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.06.016· OSTI ID:20717663

Kaspar, Petr ^[1]; Pajer, Petr ^[1]; Sedlak, David ^[1]; Tamaoki, Taiki ^[2]; Dvorak, Michal ^[1]

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1. Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo 2, 166 37 Prague 6 (Czech Republic)
2. Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1 (Canada)

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.

• OSTI ID: 20717663
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 309; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BLOOD FORMATION
GENES
LEAD SULFIDES
MYOBLASTS
ONCOGENIC VIRUSES
PHOSPHATES
PROTEINS
RNA
TRANSCRIPTION