PI3K/AKT信号通路调控Myogenin和MCK基因的表达  

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

作　　者：李晶[1] 张云生[2] 李宁[2] 胡晓湘[2] 石国庆[1] 刘守仁[1] 柳楠[3] 

机构地区：[1]石河子大学动物科技学院,石河子832003 [2]中国农业大学农业生物技术国家重点实验室,北京100193 [3]青岛农业大学动物科技学院,青岛266109

出　　处：《遗传》2013年第5期637-642,共6页Hereditas（Beijing)

基　　金：国家重点基础研究发展计划(973计划)项目(编号:2006CB102100);国家自然科学基金项目(编号:30671496)资助

摘　　要：骨骼肌分化过程受多个信号通路调控,PI3K/AKT信号通路是其中最重要的信号转导通路之一。PI3K/AKT信号通路可以调控骨骼肌分化,但在染色质水平上的调控机制还不是很清楚。文章以小鼠成肌细胞(C2C12)为研究材料,采用免疫印迹、染色质免疫共沉淀(Chromatin immunoprecipitation,ChIP)、定量PCR(Q-PCR)的方法研究PI3K/AKT信号通路调控Myogenin和MCK基因的表达。研究发现,C2C12细胞分化过程中添加PI3K/AKT信号通路激活剂处理24 h,Myogenin和MCK蛋白表达水平显著升高,组蛋白H3K27me3去甲基化酶UTX的表达也升高,H3K27me3在Myogenin基因启动子区和MCK基因启动子及增强子区的富集与对照组相比显著降低。用PI3K/AKT信号通路抑制剂处理,结果相反。因此,PI3K/AKT信号通路可能通过调控组蛋白去甲基化酶UTX的表达活性改变靶基因的H3K27me3的富集进而调控骨骼肌分化。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 C2C 12 myoblast cell line was used to investigate the expression of Myogenin and MCK genes during the skeletal muscledifferentiation. 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.

关 键 词：PI3K AKT信号通路 Myogenin基因 MCK基因 UTX H3K27me3 

分 类 号：Q75[生物学—分子生物学]