Histone Acetylation Domains Are Differentially Induced during Development of Heart Failure in Dahl Salt-Sensitive Rats.

Koji Hasegawa,Yusuke Miyazaki,Yasufumi Katanasaka,Satoshi Shimizu,Kana Shimizu,Hiromichi Wada,Tatsuya Morimoto,Nurmila Sari,Yoichi Sunagawa,Kiyoshi Mori,Masafumi Funamoto

doi:10.3390/ijms22041771

Abstract

Histone acetylation by epigenetic regulators has been shown to activate the transcription of hypertrophic response genes, which subsequently leads to the development and progression of heart failure. However, nothing is known about the acetylation of the histone tail and globular domains in left ventricular hypertrophy or in heart failure. The acetylation of H3K9 on the promoter of the hypertrophic response gene was significantly increased in the left ventricular hypertrophy stage, whereas the acetylation of H3K122 did not increase in the left ventricular hypertrophy stage but did significantly increase in the heart failure stage. Interestingly, the interaction between the chromatin remodeling factor BRG1 and p300 was significantly increased in the heart failure stage, but not in the left ventricular hypertrophy stage. This study demonstrates that stage-specific acetylation of the histone tail and globular domains occurs during the development and progression of heart failure, providing novel insights into the epigenetic regulatory mechanism governing transcriptional activity in these processes.

Highlights

Heart failure (HF) is a major health problem and a leading cause of death worldwide [1,2]
These findings suggest that the histone acetylation domain changes from the tail domain to the globular domain during the transition from the left ventricular hypertrophy (LVH) stage to the HF stage and that the formation of the p300/BRG1 complex is involved in this change in the histone acetylation domain
The results showed that H3K9 acetylation in the heart was increased around the atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) promoters in the 12w Dahl salt-sensitive (DS) rats compared with the 12w Dahl saltresistant (DR) rats

Summary

Introduction

Heart failure (HF) is a major health problem and a leading cause of death worldwide [1,2]. Epigenetic regulatory mechanisms, including histone post-translational modification, have attracted attention as key processes in HF development [3,4,5]. The main types of post-translational histone modification are acetylation and methylation. These modifications play essential roles in a variety of regulatory mechanisms and are controlled by acetyltransferase or methylase [6]. Previous research using transgenic (TG) mice that exhibited cardiac-specific p300 overexpression showed that the heart gradually enlarged, leading to heart failure, and that left ventricular remodeling after myocardial infarction was greater in these mice than in wild-type (WT)

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