c-Myb inhibits myoblast fusion

0423052 - ÚMG 2014 RIV US eng J - Journal Article
Kašpar, Petr - Ilenčíková, Kristina - Zíková, Martina - Horvath, Ondrej - Čermák, Vladimír - Bartůněk, Petr - Strnad, Hynek
c-Myb inhibits myoblast fusion.
PLoS ONE. Roč. 8, č. 10 (2013), e76742. ISSN 1932-6203. E-ISSN 1932-6203
R&D Projects: GA ČR GAP305/10/2133
Institutional support: RVO:68378050
Keywords : c-Myb * muscle cell differentiation * satellite cells
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.534, year: 2013

Satellite cells represent a heterogeneous population of stem and progenitor cells responsible for muscle growth, repair and regeneration. We investigated whether c-Myb could play a role in satellite cell biology because our previous results using satellite cell-derived mouse myoblast cell line C2C12 showed that c-Myb was expressed in growing cells and downregulated during differentiation. We detected c-Myb expression in activated satellite cells of regenerating muscle. c-Myb was also discovered in activated satellite cells associated with isolated viable myofiber and in descendants of activated satellite cells, proliferating myoblasts. However, no c-Myb expression was detected in multinucleated myotubes originated from fusing myoblasts. The constitutive expression of c-Myb lacking the 3' untranslated region (3' UTR) strongly inhibited the ability of myoblasts to fuse. The inhibition was dependent on intact c-Myb transactivation domain as myoblasts expressing mutated c-Myb in transactivation domain were able to fuse. The absence of 3' UTR of c-Myb was also important because the expression of c-Myb coding region with its 3' UTR did not inhibit myoblast fusion. The same results were repeated in C2C12 cells as well. Moreover, it was documented that 3' UTR of c-Myb was responsible for downregulation of c-Myb protein levels in differentiating C2C12 cells. DNA microarray analysis of C2C12 cells revealed that the expression of several muscle-specific genes was downregulated during differentiation of c-Myb-expressing cells, namely: ACTN2, MYH8, TNNC2, MYOG, CKM and LRRN1. A detailed qRT-PCR analysis of MYOG, TNNC2 and LRRN1 is presented. Our findings thus indicate that c-Myb is involved in regulating the differentiation program of myogenic progenitor cells as its expression blocks myoblast fusion.
Permanent Link: http://hdl.handle.net/11104/0229194