![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
|
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
1MB | |
|
PDF (Supporting Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
369kB |
| Item Type: | Article |
|---|---|
| Title: | Epigenetic switch at Atp2a2 and Myh7 gene promoters in pressure overload-induced heart failure |
| Creators Name: | Angrisano, T. and Schiattarella, G.G. and Keller, S. and Pironti, G. and Florio, E. and Magliulo, F. and Bottino, R. and Pero, R. and Lembo, F. and Avvedimento, E.V. and Esposito, G. and Trimarco, B. and Chiariotti, L. and Perrino, C. |
| Abstract: | 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 Ca(2+)ATPase (SERCA-2A) and β-myosin-heavy chain (β-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 β-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. |
| Keywords: | Chromatin, Gene Expression Profiling, Genetic Epigenesis, Genetic Promoter Regions, Heart Failure, Histones, Inbred C57BL Mice, Jumonji Domain-Containing Histone Demethylases, Lysine, Myosin Heavy Chains, Pressure, Sarcoplasmic Reticulum Calcium-Transporting ATPases, Animals, Mice |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 9 |
| Number: | 9 |
| Page Range: | e106024 |
| Date: | 2 September 2014 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0106024 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
Download Statistics
Download Statistics
