Fuso A, Cavallaro R A, Orrù L, Buttarelli F R, Scarpa S
Department of Cellular Biotechnologies and Hematology, Research Laboratory, Rome, Italy.
FEBS Lett. 2001 Nov 23;508(3):337-40. doi: 10.1016/s0014-5793(01)03030-7.
A well-characterised experimental system, the myogenin gene in C2C12 muscle cell culture, was chosen to better understand the methylation mechanism underlying the regulation of gene expression. We already demonstrated that demethylation dynamics of a specific CpG site in the 5'-flanking region of myogenin well correlates with gene expression and terminal differentiation. Here we demonstrate that S-adenosylmethionine-sulphate-p-toluenesulphonate (SAM) inhibits myogenin expression and myoblast differentiation by delaying the demethylation of specific CpG in differentiating myoblasts. These results suggest new perspectives in methylation mechanisms and the use of SAM in the partial silencing of gene expression, as it could be required in disease treatment.
为了更好地理解基因表达调控背后的甲基化机制，我们选择了一个特征明确的实验系统，即C2C12肌肉细胞培养中的肌细胞生成素基因。我们已经证明，肌细胞生成素5'侧翼区域特定CpG位点的去甲基化动态与基因表达和终末分化密切相关。在此，我们证明S-腺苷甲硫氨酸-硫酸盐-对甲苯磺酸盐（SAM）通过延迟分化成肌细胞中特定CpG的去甲基化来抑制肌细胞生成素的表达和成肌细胞分化。这些结果为甲基化机制以及SAM在基因表达部分沉默中的应用提供了新的视角，因为在疾病治疗中可能需要这种应用。
