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

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 un...

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Autores principales: Angrisano, Tiziana, Schiattarella, Gabriele Giacomo, Keller, Simona, Pironti, Gianluigi, Florio, Ermanno, Magliulo, Fabio, Bottino, Roberta, Pero, Raffaela, Lembo, Francesca, Avvedimento, Enrico Vittorio, Esposito, Giovanni, Trimarco, Bruno, Chiariotti, Lorenzo, Perrino, Cinzia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152141/
https://www.ncbi.nlm.nih.gov/pubmed/25181347
http://dx.doi.org/10.1371/journal.pone.0106024
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author Angrisano, Tiziana
Schiattarella, Gabriele Giacomo
Keller, Simona
Pironti, Gianluigi
Florio, Ermanno
Magliulo, Fabio
Bottino, Roberta
Pero, Raffaela
Lembo, Francesca
Avvedimento, Enrico Vittorio
Esposito, Giovanni
Trimarco, Bruno
Chiariotti, Lorenzo
Perrino, Cinzia
author_facet Angrisano, Tiziana
Schiattarella, Gabriele Giacomo
Keller, Simona
Pironti, Gianluigi
Florio, Ermanno
Magliulo, Fabio
Bottino, Roberta
Pero, Raffaela
Lembo, Francesca
Avvedimento, Enrico Vittorio
Esposito, Giovanni
Trimarco, Bruno
Chiariotti, Lorenzo
Perrino, Cinzia
author_sort Angrisano, Tiziana
collection PubMed
description 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.
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spelling pubmed-41521412014-09-05 Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure Angrisano, Tiziana Schiattarella, Gabriele Giacomo Keller, Simona Pironti, Gianluigi Florio, Ermanno Magliulo, Fabio Bottino, Roberta Pero, Raffaela Lembo, Francesca Avvedimento, Enrico Vittorio Esposito, Giovanni Trimarco, Bruno Chiariotti, Lorenzo Perrino, Cinzia PLoS One Research Article 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. Public Library of Science 2014-09-02 /pmc/articles/PMC4152141/ /pubmed/25181347 http://dx.doi.org/10.1371/journal.pone.0106024 Text en © 2014 Angrisano et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Angrisano, Tiziana
Schiattarella, Gabriele Giacomo
Keller, Simona
Pironti, Gianluigi
Florio, Ermanno
Magliulo, Fabio
Bottino, Roberta
Pero, Raffaela
Lembo, Francesca
Avvedimento, Enrico Vittorio
Esposito, Giovanni
Trimarco, Bruno
Chiariotti, Lorenzo
Perrino, Cinzia
Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title_full Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title_fullStr Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title_full_unstemmed Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title_short Epigenetic Switch at Atp2a2 and Myh7 Gene Promoters in Pressure Overload-Induced Heart Failure
title_sort epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4152141/
https://www.ncbi.nlm.nih.gov/pubmed/25181347
http://dx.doi.org/10.1371/journal.pone.0106024
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