Open AccessBone morphogenetic protein-2 enhances the expression of cardiac transcription factors by increasing histone H3 acetylation in H9c2 cells
Author(s) -
Min Zheng,
Jing Zhu,
Tiewei Lv,
Lingjuan Liu,
Huichao Sun,
Jie Tian
Publication year - 2013
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2013.1266
Subject(s) - chromatin immunoprecipitation , histone h3 , mef2c , biology , histone , microbiology and biotechnology , acetylation , sap30 , gata4 , transcription factor , histone h2a , gene expression , cancer research , promoter , gene , genetics
Bone morphogenetic protein (BMP)‑2 induces the expression of cardiac transcriptionfactors during early heart development, however, the underlying mechanisms forthis are not clear. Our previous studies indicated that histone acetylation iscritical in the regulation of cardiac gene expression. In the present study, thehypothesis that BMP2 enhances the expression of cardiac transcription factorsby increasing histone H3 acetylation was tested. Cultured H9c2 rat embryonic cardiacmyocytes were transfected with adenoviruses expressing human BMP2 (AdBMP2). Real‑timeRT‑PCR, western blotting, chromatin immunoprecipitation (ChIP) and colorimetricassays were employed to determine gene expression, histone H3 acetylation levelsand histone acetylase (HAT) activities. The mRNA expression levels of BMP2, GATA4,MEF2C and p300, but not of Tbx5 and GCN5, were significantly upregulated followingtransfection with AdBMP2. Similarly, the histone H3 acetylation levels were enhancedin the whole chromatin and in the promoter regions of GATA4 and MEF2C, but notTbx5, in the transfected cells. The HAT activities were also enhanced. These resultsindicate that BMP2 is able to upregulate the expression of the cardiac transcriptionfactors GATA4 and MEF2C, in part by increasing histone H3 acetylation in the promoterregions of these genes.