Background: Congenital heart diseases (CHD) remain the leading cause of death related to birth defects.A transcriptional network of genetic and epigenetic factors is accepted as a mechanistic understanding of pathogenesis in CHD.Histone acetylation, as one of the posttranslational modifications, is reversible and its level dynamically maintained by histone acetyltransferases (HATs) and deacetylases (HDACs), controlling gene expression and cellular signaling events.Nevertheless, little is known about the status ofhistone acetylation in CHD.Methods: Histone H3K9, H3K18 and H3K27 acetylation from 10 CHD patients and 5 controls were assayed by Immunohistochemistry staining.Quantitative real-time PCR was applied to detected mRNA levels of HATs including EP300, CREBBP, GCN5, PCAF, MOZ and TIP60, and HDACs including HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC9 and HDAC11.Results: H3K9 acetylation was found to increase in outflow tract in patients with CHD (p<0.05), and oppositely, H3K18 acetylation (p<0.05) and H3K27 acetylation (p<0.05) were both descending.For mRNA levels of 12 enzymes, the EP300 was revealed higher expression in CHD patients (0.982±0.060, n=39) than that in controls (0.738±0.083, n=14; p<0.05).As a cofactors of EP300, CREBBP has increased as well (1.166±0.1136, n=39; p<0.05) compared with controls (0.8201 ±0.08154, n=15).Inversely, GCN5 expression was significantly repressed in CHD patients (3.555±0.2827, n=39) compared with controls (8.953±1.413, n =18; p<0.001).There were no differences in all 7 HDACs and part HATs between CHD patients and controls (p>0.05).Correlation analysis indicated that the increase of EP300 and CREBBP was responsible to the change of H3K9 acetylation (p<0.05) but H3K18 acetylation (p>0.05) and H3K27 acetylation (p>0.05).Conclusion: Aberrant histone acetylation and abnormal enzymes expression in CHD patients imply histone acetylation and its enzymes may play an important role in the pathogenesis of congenital heart disease.