Potthoff Matthew J, Arnold Michael A, McAnally John, Richardson James A, Bassel-Duby Rhonda, Olson Eric N
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Mol Cell Biol. 2007 Dec;27(23):8143-51. doi: 10.1128/MCB.01187-07. Epub 2007 Sep 17.
Myocyte enhancer factor 2 (MEF2) transcription factors cooperate with the MyoD family of basic helix-loop-helix (bHLH) transcription factors to drive skeletal muscle development during embryogenesis, but little is known about the potential functions of MEF2 factors in postnatal skeletal muscle. Here we show that skeletal muscle-specific deletion of Mef2c in mice results in disorganized myofibers and perinatal lethality. In contrast, neither Mef2a nor Mef2d is required for normal skeletal muscle development in vivo. Skeletal muscle deficient in Mef2c differentiates and forms normal myofibers during embryogenesis, but myofibers rapidly deteriorate after birth due to disorganized sarcomeres and a loss of integrity of the M line. Microarray analysis of Mef2c null muscles identified several muscle structural genes that depend on MEF2C, including those encoding the M-line-specific proteins myomesin and M protein. We show that MEF2C directly regulates myomesin gene transcription and that loss of Mef2c in skeletal muscle results in improper sarcomere organization. These results reveal a key role for Mef2c in maintenance of sarcomere integrity and postnatal maturation of skeletal muscle.
肌细胞增强因子2（MEF2）转录因子与碱性螺旋-环-螺旋（bHLH）转录因子的MyoD家族协同作用，以驱动胚胎发育过程中的骨骼肌发育，但关于MEF2因子在出生后骨骼肌中的潜在功能知之甚少。在此我们表明，小鼠中Mef2c的骨骼肌特异性缺失会导致肌纤维紊乱和围产期致死。相比之下，Mef2a和Mef2d在体内正常骨骼肌发育中并非必需。缺乏Mef2c的骨骼肌在胚胎发育过程中分化并形成正常的肌纤维，但出生后由于肌节紊乱和M线完整性丧失，肌纤维迅速退化。对Mef2c缺失肌肉的微阵列分析确定了几个依赖于MEF2C的肌肉结构基因，包括那些编码M线特异性蛋白肌间线蛋白和M蛋白的基因。我们表明MEF2C直接调节肌间线蛋白基因转录，并且骨骼肌中Mef2c的缺失导致肌节组织不当。这些结果揭示了Mef2c在维持肌节完整性和出生后骨骼肌成熟中的关键作用。
