Bone morphogenetic protein‑2 enhances the expression of cardiac transcription factors by increasing histone H3 acetylation in H9c2 cells.
Bone morphogenetic protein‑2 enhances the expression of cardiac transcription factors by increasing histone H3 acetylation in H9c2 cells.
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骨形态发生蛋白 2 通过增加 H9c2 细胞中组蛋白 H3 乙酰化来增强心脏转录因子的表达。
DOI：
10.3892/mmr.2013.1266
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发表时间：
2013
影响因子：
3.4
通讯作者：
Jie Tian
中科院分区：
文献类型：
--
作者：
Min Zheng;Jing Zhu;Tiewei Lv;Ling;Huichao Sun;Jie Tian
骨形态发生蛋白-2(BMP-2)在心脏发育早期诱导心脏转录因子的表达，但其机制尚不清楚。我们以前的研究表明，组蛋白乙酰化在心脏基因表达的调控中起着关键作用。在本研究中，BMP2通过增加组蛋白H3乙酰化来增强心脏转录因子表达的假设得到了验证。将表达人骨形成蛋白2的腺病毒(AdBMP2)导入培养的H9c2大鼠胚胎心肌细胞。采用实时定量RT-PCR、Western blotting、染色质免疫沉淀(ChIP)和比色法检测基因表达、组蛋白H3乙酰化水平和组蛋白乙酰化酶(HAT)活性。转染AdBMP2后，BMP2、GATA4、MEF2C和p300的mRNA表达水平显著上调，而Tbx5和GCN5的mRNA表达水平无明显上调。同样，组蛋白H3乙酰化水平在整个染色质以及GATA4和MEF2C的启动子区域增强，但不是Tbx5。帽子项目的活动也得到了加强。这些结果表明，BMP2能够上调心脏转录因子GATA4和MEF2C的表达，部分是通过增加这些基因启动子区域的组蛋白和H3乙酰化。
Bone morphogenetic protein (BMP)‑2 induces the expression of cardiac transcription factors during early heart development, however, the underlying mechanisms for this are not clear. Our previous studies indicated that histone acetylation is critical in the regulation of cardiac gene expression. In the present study, the hypothesis that BMP2 enhances the expression of cardiac transcription factors by increasing histone H3 acetylation was tested. Cultured H9c2 rat embryonic cardiac myocytes were transfected with adenoviruses expressing human BMP2 (AdBMP2). Real‑time RT‑PCR, western blotting, chromatin immunoprecipitation (ChIP) and colorimetric assays were employed to determine gene expression, histone H3 acetylation levels and histone acetylase (HAT) activities. The mRNA expression levels of BMP2, GATA4, MEF2C and p300, but not of Tbx5 and GCN5, were significantly upregulated following transfection with AdBMP2. Similarly, the histone H3 acetylation levels were enhanced in the whole chromatin and in the promoter regions of GATA4 and MEF2C, but not Tbx5, in the transfected cells. The HAT activities were also enhanced. These results indicate that BMP2 is able to upregulate the expression of the cardiac transcription factors GATA4 and MEF2C, in part by increasing histone H3 acetylation in the promoter regions of these genes.
影响因子：
2.7
作者：
Sugi, Y;Yamamura, H;Markwald, RR
通讯作者：
Markwald, RR
影响因子：
2.7
作者：
Miho Yamada;J. Revelli;G. Eichele;Matt Barron;R. Schwartz
通讯作者：
Miho Yamada;J. Revelli;G. Eichele;Matt Barron;R. Schwartz