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 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.
Kaspar
Petr
P
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Flemingovo 2, 16637 Prague 6, Czech Republic.
Pajer
Petr
P
Sedlak
David
D
Tamaoki
Taiki
T
Dvorak
Michal
M
D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D051379:Mice; D008809:Mice, Inbred C3H; D017570:MyoD Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000096:biosynthesis / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020598:Proto-Oncogene Proteins c-myb / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D020598:Proto-Oncogene Proteins c-myb; C063403:myogenic factor 6