c-Myb inhibits myogenic differentiation through repression of MyoD

• Published in: Experimental cell research Vol. 309; no. 2; pp. 419 - 428
• Main Authors: Kaspar, Petr, Pajer, Petr, Sedlak, David, Tamaoki, Taiki, Dvorak, Michal
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2005; Elsevier BV
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; BLOOD FORMATION; c-Myb; Cell Count; Cell Differentiation - physiology; Cell Line; Cell–cell contact; GENES; LEAD SULFIDES; Mice; Mice, Inbred C3H; MYOBLASTS; Myoblasts - cytology; Myoblasts - metabolism; MyoD; MyoD Protein - antagonists & inhibitors; MyoD Protein - metabolism; Myogenesis; Myogenic Regulatory Factors - biosynthesis; Myogenic Regulatory Factors - genetics; ONCOGENIC VIRUSES; PHOSPHATES; Promoter Regions, Genetic; Protein Binding; PROTEINS; Proto-Oncogene Proteins c-myb - biosynthesis; Proto-Oncogene Proteins c-myb - genetics; Proto-Oncogene Proteins c-myb - physiology; RNA; TRANSCRIPTION; PBS; MEF2; Cell–cell contact; RSV; c-Myb; HDAC1; MyoD; AMV; Myogenesis
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2005.06.016

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.