Background: Epigenetic regulatory mechanisms such as histone post-translational modifications are involved in the heart failure (HF). Although the acetylation of tail domains, such as H3K9, has been extensively studied, that of H3K122, the globular domain, has received much less attention. The H3K122 acetylation directly activates transcription by destabilizing histone-DNA binding. However, the mechanism of these domains acetylation in the development of HF remains unknown. 
Methods and Results: Cultured cardiomyocytes prepared from neonatal rats were treated with phenylephrine (PE). PE increased the acetylation of H3K9 and H3K122. The acetylation of H3K9 and H3K122 on the promoters of BNP and b-MHC, which are hypertrophic reaction genes, was increased in cardiomyocyte hypertrophy. In Dahl-salt sensitive rats, a heart failure model, in vivo ChIP assays revealed that the acetylation of H3K9 on the promoters of BNP and b-MHC was increased in left ventricular hypertrophy (LVH), while that of H3K122 was increased in HF. On the other hand, there was no difference in the amount of transcriptional coactivator p300 recruitment in LVH and HF. Interestingly, IP -WB showed that binding of p300 with BRG1, a key component of the SWI/SNF complex, was enhanced in HF. The recruitment of BRG1 was increased in HF compared to LVH. Moreover, PFI-3, a BRG1 inhibitor, suppressed PE-induced increases in the acetylation of H3K122 in cultured cardiomyocytes.
Conclusion: This study shows that the acetylation of H3K122 is enhanced via the interaction of p300 with BRG1 in heart failure.