基础医学与临床 ›› 2016, Vol. 36 ›› Issue (9): 1179-1186.

• 研究论文 •    下一篇

Islet-1诱导成纤维细胞C3H10T1/2向心肌细胞分化过程中组蛋白乙酰化与DNA甲基化在GATA4启动子区的关系

王越1,朱静2,田杰3,许皓2,易勤2,赖星宇2   

  1. 1. 重庆市渝中区中山二路136号重庆医科大学附属儿童医院
    2. 重庆医科大学附属儿童医院
    3. 重庆医科大学及附属儿童医院
  • 收稿日期:2015-08-17 修回日期:2015-12-01 出版日期:2016-09-05 发布日期:2016-08-30
  • 通讯作者: 王越 E-mail:wangyue132106@163.com
  • 基金资助:
    MSCs向心肌细胞分化中特异基因的DNA甲基化/组蛋白乙酰化交互调控作用

Relationship between histone acetylation and DNA methylation in GATA4 promoter region during Islet-1 induced differentiation of C3H10T1/2 cells specifically into cardiomyocytes

  • Received:2015-08-17 Revised:2015-12-01 Online:2016-09-05 Published:2016-08-30

摘要: 目的 研究在Islet-1诱导间充质干细胞C3H10T1/2向心肌细胞特异分化过程中的心肌早期发育相关基因GATA4启动子区域组蛋白乙酰化与DNA甲基化的相互作用关系。方法 构建过表达Islet-1细胞模型,在GATA4基因表达过程中,用染色质免疫共沉淀技术(CHIP)检测其启动子区组蛋白H3K9乙酰化的时序性变化;甲基化特异性PCR技术(MSP)检测其启动子区CpG岛甲基化的时序性变化,明确两者之间相互作用的关系。结果 随着Islet-1诱导C3H10T1/2向心肌细胞特异分化的时间延长,GATA4基因的表达增高(P<0.05),其启动子区第2个CpG位点组蛋白H3K9乙酰化的水平升高(P<0.05),DNA甲基化水平降低(P<0.05)。结论 Islet-1诱导C3H10T1/2细胞向心肌细胞特异分化过程中,组蛋白乙酰化和DNA甲基化在调控心肌特异早期转录因子GATA4表达过程中存在相互拮抗作用,从而促其表达呈时序性变化。

关键词: Islet-1, 组蛋白乙酰化, DNA甲基化, 间充质干细胞, 心肌细胞

Abstract: Objective To research the interaction between early myocardial developmental gene GATA4 histone acetylation and its DNA methylation of promoter during Islet-1 inducing the mesenchymal stem cells of C3H10T1/2 cells to differentiate specifically into cardiomyocytes.Method Constructing the model of Islet-1 over-expression cells,in the process of GATA4 gene expression by using chromatin immunoprecipitation(CHIP)to detecte histone H3K9 acetylation sequential changes of its promoter region and using the methylation-specific PCR(MSP)to detect methylation sequential changes in CpG island of its promoter region,to elucidate the interaction between the both.Result With prolongation of time during Islet-1 inducing C3H10T1/2 to differentiate specifically into cardiomyocytes,the expression of the GATA4 gene increased(P<0.05),the level of histone H3K9 acetylation raised(P<0.05),while the DNA methylation level decreased in the second CpG site of its promoter(P<0.05).Conclusion During the Islet-1 promotes cells into cardiac-specific differentiation process,it is indicated that histone acetylation and DNA methylation exist mutual antagonism in regulation of the process of early myocardial specific transcription factor GATA4 expression,which promoted its sequential expression.

Key words: Islet-1, histone acetylation, DNA methylation, mesenchymal stem cells, cardiomyocyte

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