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[由PI3K/AKT通路调控的肌细胞生成素和肌酸激酶基因的表达]

[Expression of Myogenin and MCK genes regulated by PI3K/AKT pathway].

作者信息

Li Jing, Zhang Yun-Sheng, Li Ning, Hu Xiao-Xiang, Shi Guo-Qing, Liu Shou-Ren, Liu Nan

机构信息

Shihezi University, Shihezi, China.

出版信息

Yi Chuan. 2013 May;35(5):637-42. doi: 10.3724/sp.j.1005.2013.00637.

Abstract

Many intracellular signaling pathways regulate skeletal muscle differentiation. Among them, PI3K/AKT pathway plays an important role. But the mechanisms of chromatin regulation remain unclear. In this study, the murine C2C12 myoblast cell line was used to investigate the expression of Myogenin and MCK genes during the skeletal muscle differentiation. Western blotting analysis showed that the expression of Myogenin and MCK protein was increased significantly after PI3K/AKT activator treatment for 24 h during the C2C12 cell differentiation and the expression of H3K27me3 demethylase UTX was also increased. Chromatin immunoprecipitation (ChIP) and quantitative PCR (Q-PCR) analysis showed that the enrichment of H3K27me3 on the promoter regions of Myogenin and MCK genes and the enhancer region of MCK gene were decreased. It was opposite to the PI3K/AKT inhibitor treatment. We concluded that the PI3K/AKT pathway maybe regulate skeletal muscle differentiation by regulating the expression of UTX gene to change the enrichment of H3K27me3 on the target genes.

摘要

许多细胞内信号通路调节骨骼肌分化。其中,PI3K/AKT通路发挥着重要作用。但其染色质调控机制仍不清楚。在本研究中,使用小鼠C2C12成肌细胞系来研究骨骼肌分化过程中肌细胞生成素(Myogenin)和肌酸激酶(MCK)基因的表达。蛋白质免疫印迹分析表明,在C2C12细胞分化过程中,用PI3K/AKT激活剂处理24小时后,肌细胞生成素和MCK蛋白的表达显著增加,并且H3K27me3去甲基化酶UTX的表达也增加。染色质免疫沉淀(ChIP)和定量PCR(Q-PCR)分析表明,肌细胞生成素和MCK基因启动子区域以及MCK基因增强子区域上H3K27me3的富集减少。这与PI3K/AKT抑制剂处理的情况相反。我们得出结论,PI3K/AKT通路可能通过调节UTX基因的表达来改变靶基因上H3K27me3的富集,从而调节骨骼肌分化。

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