c-Myb inhibits myogenic differentiation through repression of MyoD
- Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo 2, 166 37 Prague 6 (Czech Republic)
- 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, Vol. 309, Issue 2; Other Information: DOI: 10.1016/j.yexcr.2005.06.016; PII: S0014-4827(05)00294-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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