title: Genome-wide analysis of histone marks identifying an epigenetic signature of promoters and enhancers underlying cardiac hypertrophy.
abstract: Cardiac hypertrophy, initially an adaptive response of the myocardium to stress, can progress to heart failure. The epigenetic signature underlying this phenomenon is poorly understood. Here, we report on the genome-wide distribution of seven histone modifications in adult mouse cardiomyocytes subjected to a prohypertrophy stimulus in vivo. We found a set of promoters with an epigenetic pattern that distinguishes specific functional classes of genes regulated in hypertrophy and identified 9,207 candidate active enhancers whose activity was modulated. We also analyzed the transcriptional network within which these genetic elements act to orchestrate hypertrophy gene expression, finding a role for myocyte enhancer factor (MEF)2C and MEF2A in regulating enhancers. We propose that the epigenetic landscape is a key determinant of gene expression reprogramming in cardiac hypertrophy and provide a basis for understanding the role of chromatin in regulating this phenomenon.
authors.affiliation: Humanitas Clinical and Research Center, 20089 Rozzano, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Papait
authors.forename: Paola
authors.initials: P
authors.lastname: Cattaneo
authors.forename: Paolo
authors.initials: P
authors.lastname: Kunderfranco
authors.forename: Carolina
authors.initials: C
authors.lastname: Greco
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Carullo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Guffanti
authors.forename: Valentina
authors.initials: V
authors.lastname: Viganò
authors.forename: Giuliano Giuseppe
authors.initials: GG
authors.lastname: Stirparo
authors.forename: Michael V G
authors.initials: MV
authors.lastname: Latronico
authors.forename: Gerd
authors.initials: G
authors.lastname: Hasenfuss
authors.forename: Ju
authors.initials: J
authors.lastname: Chen
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Condorelli
mesh_terms: D000107:Acetylation; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006657:Histones / Q000378:metabolism*; D008745:Methylation; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D006657:Histones; D014157:Transcription Factors
keywords: epigenetic regulation; histone acetylation; histone methylation