Bone morphogenetic protein-2 enhances the expression of cardiac transcription factors by increasing histone H3 acetylation in H9c2 cells

Abstract

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 histoneH3 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, histoneH3 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 histoneH3 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 histoneH3 acetylation in the promoter regions of these genes.