title: Epigenetic switch at atp2a2 and myh7 gene promoters in pressure overload-induced heart failure.
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 Ca2+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.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy; Department of Biology, Federico II University, Naples, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Angrisano
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Gabriele Giacomo
authors.initials: GG
authors.lastname: Schiattarella
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Keller
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy; Department of Medicine, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pironti
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Florio
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Magliulo
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Bottino
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Pero
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lembo
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Enrico Vittorio
authors.initials: EV
authors.lastname: Avvedimento
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, Federico II University, Naples, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Chiariotti
authors.affiliation: Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Perrino
mesh_terms: D000818:Animals; D002843:Chromatin / Q000378:metabolism; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018995:Myosin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D011312:Pressure; D011401:Promoter Regions, Genetic; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006657:Histones; C551613:Myh7 protein, mouse; C547579:FBXL11 protein, mouse; D056484:Jumonji Domain-Containing Histone Demethylases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D018995:Myosin Heavy Chains; C506947:Atp2a2 protein, mouse; D008239:Lysine