p300-Mediated Histone Acetylation is Essential for the Regulation of GATA4 and MEF2C by BMP2 in H9c2 Cells
p300-Mediated Histone Acetylation is Essential for the Regulation of GATA4 and MEF2C by BMP2 in H9c2 Cells
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p300 介导的组蛋白乙酰化对于 H9c2 细胞中 BMP2 调节 GATA4 和 MEF2C 至关重要
DOI：
10.1007/s12012-013-9212-4
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发表时间：
2013-04
期刊：
影响因子：
--
通讯作者：
Zheng M,Tian Jie
中科院分区：
文献类型：
--
作者：
Zheng M,Tian Jie
组蛋白乙酰化酶（HAT）p300在心脏基因表达调控中起重要作用。在心脏发育过程中，骨形态发生蛋白（BMP）-2诱导心脏转录因子的表达。然而，其潜在的分子机制尚不清楚。在本研究中，我们测试的假设，即p300介导的组蛋白乙酰化是必不可少的调节心脏转录因子的BMP 2。培养的大鼠H9 c2胚胎心肌细胞（H9 c2细胞）转染重组腺病毒表达人BMP 2（AdBMP 2）与或不与姜黄素，一个特定的p300-HAT抑制剂。实时定量RT-PCR分析表明，姜黄素基本上抑制了AdBMP 2诱导的和基础的心脏转录因子GATA 4和MEF 2C的表达水平，但不是Tbx 5。同样，染色质免疫沉淀（ChIP）分析表明，姜黄素抑制AdBMP 2诱导和基础组蛋白H3乙酰化水平的GATA 4和MEF 2C的启动子区域，但不是Tbx 5。此外，姜黄素选择性地抑制AdBMP 2诱导的HAT p300的表达，但不抑制HAT GCN 5在H9 c2细胞中的表达。这些数据表明，姜黄素抑制组蛋白H3乙酰化减少了BMP 2诱导的GATA 4和MEF 2C的表达，表明p300介导的组蛋白乙酰化对于H9 c2细胞中BMP 2调节GATA 4和MEF 2C是必不可少的。
Histone acetylase (HAT) p300 plays an important role in the regulation of cardiac gene expression. During cardiac development, bone morphogenetic protein (BMP)-2 induces the expression of cardiac transcription factors. However, the underlying molecular mechanism(s) is not clear. In the present study, we tested the hypothesis that p300-mediated histone acetylation was essential for the regulation of cardiac transcription factors by BMP2. Cultured rat H9c2 embryonic cardiac myocytes (H9c2 cells) were transfected with recombinant adenoviruses expressing human BMP2 (AdBMP2) with or without curcumin, a specific p300-HAT inhibitor. Quantitative real-time RT-PCR analysis showed that curcumin substantially inhibited both AdBMP2-induced and basal expression levels of cardiac transcription factors GATA4 and MEF2C, but not Tbx5. Similarly, chromatin immunoprecipitation (ChIP) analysis showed that curcumin inhibited both AdBMP2-induced and basal histone H3 acetylation levels in the promoter regions of GATA4 and MEF2C, but not of Tbx5. In addition, curcumin selectively suppressed AdBMP2-induced expression of HAT p300, but not HAT GCN5 in H9c2 cells. The data indicated that inhibition of histone H3 acetylation with curcumin diminished BMP2-induced expression of GATA4 and MEF2C, suggesting that p300-mediated histone acetylation was essential for the regulation of GATA4 and MEF2C by BMP2 in H9c2 cells.
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发表时间：
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期刊：
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