Université de Toulouse-Paul Sabatier, Centre de Biologie du Développement, Toulouse, France.
PLoS One. 2011;6(10):e25427. doi: 10.1371/journal.pone.0025427. Epub 2011 Oct 10.
In vertebrates, skeletal myogenesis involves the sequential activation of myogenic factors to lead ultimately to the differentiation into slow and fast muscle fibers. How transcriptional co-regulators such as arginine methyltransferases PRMT4/CARM1 and PRMT5 control myogenesis in vivo remains poorly understood. Loss-of-function experiments using morpholinos against PRMT4/CARM1 and PRMT5 combined with in situ hybridization, quantitative polymerase chain reaction, as well as immunohistochemistry indicate a positive, but differential, role of these enzymes during myogenesis in vivo. While PRMT5 regulates myod, myf5 and myogenin expression and thereby slow and fast fiber formation, PRMT4/CARM1 regulates myogenin expression, fast fiber formation and does not affect slow fiber formation. However, our results show that PRMT4/CARM1 is required for proper slow myosin heavy chain localization. Altogether, our results reveal a combinatorial role of PRMT4/CARM1 and PRMT5 for proper myogenesis in zebrafish.
在脊椎动物中，骨骼肌发生涉及肌生成因子的顺序激活，最终导致慢肌和快肌纤维的分化。然而，像精氨酸甲基转移酶 PRMT4/CARM1 和 PRMT5 这样的转录共调节因子如何在体内控制肌发生仍然知之甚少。使用针对 PRMT4/CARM1 和 PRMT5 的 morpholino 的功能丧失实验，结合原位杂交、定量聚合酶链反应以及免疫组织化学，表明这些酶在体内肌发生过程中具有积极但不同的作用。虽然 PRMT5 调节 myod、myf5 和 myogenin 的表达，从而调节慢肌和快肌纤维的形成，但 PRMT4/CARM1 调节 myogenin 的表达、快肌纤维的形成，而不影响慢肌纤维的形成。然而，我们的结果表明 PRMT4/CARM1 是正确的慢肌球蛋白重链定位所必需的。总之，我们的结果揭示了 PRMT4/CARM1 和 PRMT5 在斑马鱼中正确肌发生的组合作用。
