Effect of CBP/P300-mediated H3K9 acetylation on GATA4 expression in fetal mouse myocardocytes

蒋大贵; 刘玲娟; 吕铁伟; 田杰; 孙慧超

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Effect of CBP/P300-mediated H3K9 acetylation on GATA4 expression in fetal mouse myocardocytes

更新时间：2026-01-09

- Effect of CBP/P300-mediated H3K9 acetylation on GATA4 expression in fetal mouse myocardocytes
- Journal of Army Medical University Vol. 38, Issue 18, Pages: 2018-2022(2016)
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  CLC： R321.5;R322.11;R394.2
- Published：2016
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蒋大贵,刘玲娟,吕铁伟,田杰,孙慧超.CBP/P300介导的组蛋白H3K9乙酰化修饰对GATA4表达的影响[J].陆军军医大学学报(原第三军医大学学报),2016,38(18):2018-2022.

　Jiang Dagui,Liu Lingjuan,Lyu Tiewei,Tian Jie,Sun Huichao.Effect of CBP/P300-mediated H3K9 acetylation on GATA4 expression in fetal mouse myocardocytes[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(18):2018-2022.
蒋大贵,刘玲娟,吕铁伟,田杰,孙慧超.CBP/P300介导的组蛋白H3K9乙酰化修饰对GATA4表达的影响[J].陆军军医大学学报(原第三军医大学学报),2016,38(18):2018-2022. DOI：

　Jiang Dagui,Liu Lingjuan,Lyu Tiewei,Tian Jie,Sun Huichao.Effect of CBP/P300-mediated H3K9 acetylation on GATA4 expression in fetal mouse myocardocytes[J].J Amry Med Univ (J Third Mil Med Univ),2016,38(18):2018-2022. DOI：

摘要

目的明确GATA4在小鼠胚胎心脏发育过程中的时序表达，并阐明其组蛋白修饰调控机制。方法选取胎龄11.5 d （E11.5）至新生0.5 d胎鼠心脏，RT-PCR检测胎鼠心肌细胞中GATA4 mRNA表达水平， CHIP-QPCR检测GATA4启动子区组蛋白H3K9ac水平及与CBP/P300的结合水平。用CBP30干预心肌祖细胞，RT-PCR检测心肌祖细胞在不同浓度CBP30（0.5、1、2、4 μmol/L）干预不同时间点（6、12、24、36 h）后GATA4 mRNA表达水平，CHIP-QPCR检测心肌祖细胞中GATA4启动子区组蛋白H3K9ac水平及与CBP/P300的结合水平。结果 ①小鼠胚胎心脏发育过程中GATA4表达量，E14.5明显高于E11.5（P0.05）；CHIP结果显示E14.5GATA4启动子区组蛋白H3K9ac水平高于E11.5（P0.05）；E14.5与CBP/P300的结合水平亦高于E11.5（P0.05）。②CBP30干预心肌祖细胞后，GATA4表达量较对照组明显降低（P0.05）。CHIP结果显示CBP30组GATA4启动子区组蛋白H3K9ac水平及与CBP/P300的结合水平较对照组显著降低（P0.05）。结论 CBP/P300可通过介导组蛋白H3K9乙酰化修饰参与调控GATA4在小鼠胚胎心脏发育过程中的时序表达。

Abstract

Objective To investigate the temporal expression of GATA4 in the development process of mouse embryonic heart and elucidate the underlying mechanism of histone modification. Methods RT-PCR was used to detect the expression of GATA4 in fetal mouse hearts from gestational age E11.5 d to postnatal 0.5 d. ChIP-QPCR was employed to the expression level of histone marker H3K9ac in GATA4 promoter region and the binding level of CBP/P300. After the cardiac progenitor cells were treated with CBP30 at different concentrations (0.5

1.0

2.0 and 4.0 μmol/L) for different time periods (6

24 and 48 h)

the expression levels of GATA4 mRNA and H3K9ac

and the binding level were measured again. Results ①The expression level of GATA4 mRNA was significantly higher at E11.5 than at E14.5 (P0.05). ChIP assay demonstrated that the expression level of H3K9ac in GATA4 promoter region was higher at E14.5 than at E11.5 (P0.05)

and the binding of CBP/P300 to GATA4 promoter region was stronger at E14.5 than at E11.5 (P0.05). ②Compared with control group

CBP30 resulted in an obvious decrease in GATA4 expression in cardiac progenitor cells (P0.05). In CBP30 treated cells group

all the tested markers above mention were decreased dramatically

compared to control group (P0.05). Conclusion CBP/P300 is involved in the GATA4 regulation through mediating H3K9 acetylation during the heart development in mice.

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