title: Methylome analysis reveals alterations in DNA methylation in the regulatory regions of left ventricle development genes in human dilated cardiomyopathy.
abstract: Dilated cardiomyopathy (DCM) is one of the main causes of heart failure (called cardiomyopathies) in adults. Alterations in epigenetic regulation (i.e., DNA methylation) have been implicated in the development of DCM. Here, we identified a total of 1828 differentially methylated probes (DMPs) using the Infinium 450K HumanMethylation Bead chip by comparing the methylomes between 18 left ventricles and 9 right ventricles. Alterations in DNA methylation levels were observed mainly in lowly methylated regions corresponding to promoter-proximal regions, which become hypermethylated in severely affected left ventricles. Subsequent mRNA microarray analysis showed that the effect of DNA methylation on gene expression regulation is not unidirectional but is controlled by the functional sub-network context. DMPs were significantly enriched in the transcription factor binding sites (TFBSs) we tested. Alterations in DNA methylation were specifically enriched in the cis-regulatory regions of cardiac development genes, the majority of which are involved in ventricular development (e.g., TBX5 and HAND1).
authors.affiliation: Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Chuncheon 24341, South Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Jo
authors.affiliation: Division of Structural and Functional Genomics, Center of Genome Science, National Research Institute of Health, Chuncheongbuk-do 28159, South Korea.
authors.forename: In-Uk
authors.initials: IU
authors.lastname: Koh
authors.affiliation: Division of Structural and Functional Genomics, Center of Genome Science, National Research Institute of Health, Chuncheongbuk-do 28159, South Korea.
authors.forename: Jae-Bum
authors.initials: JB
authors.lastname: Bae
authors.affiliation: Division of Structural and Functional Genomics, Center of Genome Science, National Research Institute of Health, Chuncheongbuk-do 28159, South Korea.
authors.forename: Ho-Yeong
authors.initials: HY
authors.lastname: Yu
authors.affiliation: Division of Cardiology, Cardiac and Vascular Center, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon 51353, South Korea.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
authors.affiliation: Division of Cardiology, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 44033, South Korea.
authors.forename: Jae-Joong
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
authors.forename: Murim
authors.initials: M
authors.lastname: Choi
authors.affiliation: Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Chuncheon 24341, South Korea. Electronic address: schoi@kangwon.ac.kr.
authors.forename: Sun Shim
authors.initials: SS
authors.lastname: Choi
mesh_terms: D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D002460:Cell Line; D016000:Cluster Analysis; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015894:Genome, Human; D006352:Heart Ventricles / Q000378:metabolism; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012045:Regulatory Sequences, Nucleic Acid
keywords: DNA methylation; Differentially methylated probes; Dilated cardiomyopathy; Illumina 450K chip