Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure

被引：36

作者：

Angrisano, Tiziana ^{[1
,2
]}

Schiattarella, Gabriele Giacomo ^{[3
]}

Keller, Simona ^{[1
]}

Pironti, Gianluigi ^{[3
,4
]}

Florio, Ermanno ^{[1
]}

Magliulo, Fabio ^{[3
]}

Bottino, Roberta ^{[3
]}

Pero, Raffaela ^{[1
]}

Lembo, Francesca ^{[1
]}

Avvedimento, Enrico Vittorio ^{[1
]}

Esposito, Giovanni ^{[3
]}

Trimarco, Bruno ^{[3
]}

Chiariotti, Lorenzo ^{[1
]}

Perrino, Cinzia ^{[3
]}

机构：

[1] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy

[2] Univ Naples Federico II, Dept Biol, Naples, Italy

[3] Univ Naples Federico II, Dept Adv Biomed Sci, Naples, Italy

[4] Duke Univ, Med Ctr, Dept Med, Durham, NC USA

来源：

PLOS ONE | 2014年 / 9卷 / 09期

关键词：

CHROMATIN MODIFICATIONS; CARDIAC DYSFUNCTION; DNA METHYLATION; MECHANICAL-STRESS; EXPRESSION; HYPERTROPHY; DISEASE;

D O I：

10.1371/journal.pone.0106024

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Re-induction of fetal genes and/or re-expression of postnatal genes represent hallmarks of pathological cardiac remodeling, and are considered important in the progression of the normal heart towards heart failure (HF). Whether epigenetic modifications are involved in these processes is currently under investigation. Here we hypothesized that histone chromatin modifications may underlie changes in the gene expression program during pressure overload-induced HF. We evaluated chromatin marks at the promoter regions of the sarcoplasmic reticulum Ca2+ ATPase (SERCA-2A) and beta-myosin-heavy chain (beta-MHC) genes (Atp2a2 and Myh7, respectively) in murine hearts after one or eight weeks of pressure overload induced by transverse aortic constriction (TAC). As expected, all TAC hearts displayed a significant reduction in SERCA-2A and a significant induction of beta-MHC mRNA levels. Interestingly, opposite histone H3 modifications were identified in the promoter regions of these genes after TAC, including H3 dimethylation (me2) at lysine (K) 4 (H3K4me2) and K9 (H3K9me2), H3 trimethylation (me3) at K27 (H3K27me3) and dimethylation (me2) at K36 (H3K36me2). Consistently, a significant reduction of lysine-specific demethylase KDM2A could be found after eight weeks of TAC at the Atp2a2 promoter. Moreover, opposite changes in the recruitment of DNA methylation machinery components (DNA methyltransferases DNMT1 and DNMT3b, and methyl CpG binding protein 2 MeCp2) were found at the Atp2a2 or Myh7 promoters after TAC. Taken together, these results suggest that epigenetic modifications may underlie gene expression reprogramming in the adult murine heart under conditions of pressure overload, and might be involved in the progression of the normal heart towards HF.

引用

页数：8

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