Abstract：OBJECTIVE: To study the expression of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in children with tetralogy of Fallot (TOF), and to investigate the role of histone acetylation and acetylation-related enzymes in the pathogenesis of TOF. METHODS: Myocardial tissue samples in the TOF group were obtained from 46 children with TOF who underwent radical operation, and myocardial tissue samples in the control group were obtained from 16 children who suffered accidental deaths and had no cardiac anomalies as shown by autopsy. The acetylation of H3K9, H3K18 and H3K27 was evaluated by immunohistochemistry. The mRNA expression of HATs and HDACs in the myocardium was measured by real-time PCR. The correlation between mRNA expression of HATs and HDACs and histone acetylation was analyzed. RESULTS: Compared with the control group, the TOF group showed significantly increased acetylation of H3K9 (P=0.0165) and significantly decreased acetylation of H3K18 (P=0.0048) and H3K27 (P=0.0084). As to 4 HATs and 6 HDACs, the mRNA expression of EP300 and CBP was significantly higher in the TOF group than in the control group (P=0.025; P=0.017), and there was no significant difference in the mRNA expression of other HATs and HDACs between the two groups. The correlation analysis revealed a positive correlation between H3K9 acetylation and mRNA expression of EP300 (r=0.71, P<0.01) and CBP (r=0.72, P<0.01). CONCLUSIONS: Upregulated mRNA expression of EP300 and CBP may be associated with increased H3K9 acetylation, suggesting that EP300 and CBP might affect cardiac development by regulating H3K9 acetylation.
XU Jun,LIN Yi-Xiang,GU Ruo-Yi et al. Histone acetylation and expression of acetylation-related enzymes in children with tetralogy of Fallot[J]. CJCP, 2013, 15(10): 817-821.
Kim YS, Kim MJ, Koo TH, Kim JD, Koun S, Ham HJ. Histone deacetylase is required for the activation of Wnt/beta-catenin signaling crucial for heart valve formation in zebrafish embryos[J]. Biochem Biophys Res Commun, 2012, 423(1): 140-146.
[1]
Hoffman JI, Kaplan S. The incidence of congenital heart disease[J]. J Am Coll Cardiol, 2002, 39(12): 1890-1900.
Trivedi CM, Lu MM, Wang Q, Epstein JA. Transgenic overexpression of Hdac3 in the heart produces increased postnatal cardiac myocyte proliferation but does not induce hypertrophy[J]. J Biol Chem, 2008, 283(39): 26484-26489.
[7]
Sun H, Yang X, Zhu J, Lv T, Chen Y, Chen G, et al. Inhibition of p300-HAT results in a reduced histone acetylation and down-regulation of gene expression in cardiac myocytes[J]. Life Sci, 2010, 87(23-26): 707-714.
[8]
Voss AK, Vanyai HK, Collin C, Dixon MP, McLennan BN, Scambler P, et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome[J]. Dev Cell, 2012, 23(3): 652-663.
[9]
Singh N, Trivedi CM, Lu M, Mullican SE, Lazar MA, Epstein JA. Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract[J]. Circ Res, 2011, 109(11): 1240-1249.
[10]
Wakefield L, Cornish V, Broackes-Carter F, Sim E. Arylamine N-acetyltransferase 2 expression in the developing heart[J]. J Histochem Cytochem, 2005, 53(5): 583-592.
[16]
Chen G, Zhu J, Lv T, Wu G, Sun H, Huang X, et al. Spatiotemporal expression of histone acetyltransferases, p300 and CBP, in developing embryonic hearts[J]. J Biomed Sci, 2009, 16: 24.
[11]
Vallaster M, Vallaster CD, Wu SM. Epigenetic mechanisms in cardiac development and disease[J]. Acta Biochim Biophys Sin, 2012, 44(1): 92-102.
[12]
Van Weerd JH, Koshiba-Takeuchi K, Kwon C, Takeuchi JK. Epigenetic factors and cardiac development[J]. Cardiovasc Res, 2011, 91(2): 203-211.
Kim YS, Kim MJ, Koo TH, Kim JD, Koun S, Ham HJ. Histone deacetylase is required for the activation of Wnt/beta-catenin signaling crucial for heart valve formation in zebrafish embryos[J]. Biochem Biophys Res Commun, 2012, 423(1): 140-146.
[18]
Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, et al. Environmental epigen etics: prospects for studying epigenetic mediation of exposure-response relationships[J]. Hum Genet, 2012, 131(10): 1565-1589.
[15]
Trivedi CM, Lu MM, Wang Q, Epstein JA. Transgenic overexpression of Hdac3 in the heart produces increased postnatal cardiac myocyte proliferation but does not induce hypertrophy[J]. J Biol Chem, 2008, 283(39): 26484-26489.
[16]
Chen G, Zhu J, Lv T, Wu G, Sun H, Huang X, et al. Spatiotemporal expression of histone acetyltransferases, p300 and CBP, in developing embryonic hearts[J]. J Biomed Sci, 2009, 16: 24.
