title: p300-mediated histone acetylation is essential for the regulation of GATA4 and MEF2C by BMP2 in H9c2 cells.
abstract: 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.
authors: Department of Cardiology, Children's Hospital of Chongqing Medical University, 136 Zhongshan 2nd Road, Yu Zhong District, Chongqing, 400014, People's Republic of China, zhengmin626@126.com.
authors: Min
authors: M
authors: Zheng
authors: Jing
authors: J
authors: Zhu
authors: Tiewei
authors: T
authors: Lu
authors: Lingjuan
authors: L
authors: Liu
authors: Huichao
authors: H
authors: Sun
authors: Zhenguo
authors: Z
authors: Liu
authors: Jie
authors: J
authors: Tian
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology; D050881:E1A-Associated p300 Protein / Q000502:physiology*; D050991:GATA4 Transcription Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D006657:Histones / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D064326:MEF2 Transcription Factors / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D014162:Transfection / Q000379:methods
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D050991:GATA4 Transcription Factor; C084365:Gata4 protein, rat; D006657:Histones; D064326:MEF2 Transcription Factors; C578042:MEF2C protein, rat; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat; D003474:Curcumin