Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients

Sharma, Priyanka; Garg, Gaurav; Kumar, Arun; Mohammad, Farhan; Kumar, Sudha Ramesh; Tanwar, Vinay Singh; Sati, Satish; Sharma, Abhay; Karthikeyan, Ganesan; Brahmachari, Vani; Sengupta, Shantanu

doi:10.1016/j.gene.2014.02.034

Cited by 92 publications

(60 citation statements)

References 52 publications

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“…The spectrum of applications for NGS-based profiling includes genome-wide analysis of DNA methylation patterns, post-translational modifications of histones and the coding and non-coding transcriptome, on a genome-wide scale. The impact of epigenetic changes such as DNA methylation and histone modification has been better documented in the pathogenesis of other human diseases [33][34][35][36], while the application of genomic technologies in human PAH samples are relatively limited. To date, except for a few studies [37][38][39][40], the approaches employed to delineate the disease mechanisms in PAH have not provided a global perspective of the molecular network underlying the disease phenotype.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

2016

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Pulmonary arterial hypertension (PAH) is a severe and progressive disease, characterised by high pulmonary artery pressure that usually culminates in right heart failure. Recent findings of alterations in the DNA methylation state of superoxide dismutase 2 and granulysin gene loci; histone H1 levels; aberrant expression levels of histone deacetylases and bromodomain-containing protein 4; and dysregulated microRNA networks together suggest the involvement of epigenetics in PAH pathogenesis. Thus, PAH pathogenesis evidently involves the interplay of a predisposed genetic background, epigenetic state and injurious events. Profiling the genome-wide alterations in the epigenetic mechanisms, such as DNA methylation or histone modification pattern in PAH vascular cells, may explain the great variability in susceptibility and disease severity that is frequently associated with pronounced remodelling and worse clinical outcome. Moreover, the influence of genetic predisposition and the acquisition of epigenetic alterations in response to environmental cues in PAH progression and establishment has largely been unexplored on a genome-wide scale. In order to gain insights into the molecular mechanisms leading to the development of PAH and to design novel therapeutic strategies, high-throughput approaches have to be adopted to facilitate systematic identification of the disease-specific networks using next-generation sequencing technologies, the application of these technologies in PAH has been relatively trivial to date. @ERSpublications An epigenetic component is hypothesised in PAH: an overview of the current literature and future perspectives

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Section: Discussionmentioning

confidence: 99%

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

2016

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“…It plays a crucial role in cellular differentiation (Mikkelsen et al, 2007;Wei et al, 2009;Young et al, 2011;Xie et al, 2013) and diseases (Shen et al, 2013;Roos-Araujo et al, 2014;Sharma et al, 2014). Epigenetics consists of DNA methylation, histone modifications, chromatin remodeling, and RNA interference, etc.…”

Section: Introductionmentioning

confidence: 99%

Association analysis between the distributions of histone modifications and gene expression in the human embryonic stem cell

Zuo

et al. 2016

Gene

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“…Emerging data show that aberrant DNA methylation patterns play an important role in cardiovascular disease, including atherogenesis (54), coronary artery disease (44,45), dilated cardiomyopathy (24), and heart failure (29,36,37). Furthermore, DNA methylation regulates the expression of myosin heavy chain 7 (Myh7), a sarcomere protein important for cardiac contractility (8).…”

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cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes

Fang

Robinson

Wang-Hu

et al. 2015

American Journal of Physiology-Cell Physiology

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-cAMP is a highly regulated secondary messenger involved in many biological processes. Chronic activation of the cAMP pathway by catecholamines results in cardiac hypertrophy and fibrosis; however, the mechanism by which elevated cAMP leads to cardiomyopathy is not fully understood. To address this issue, we increased intracellular cAMP levels in HL-1 cardiomyocytes, a cell line derived from adult mouse atrium, using either the stable cAMP analog N 6 ,2=-O-dibutyryladenosine 3=,5=-cyclic monophosphate (DBcAMP) or phosphodiesterase (PDE) inhibitors caffeine and theophylline. Elevated cAMP levels increased cell size and altered expression levels of cardiac genes and micro-RNAs associated with hypertrophic cardiomyopathy (HCM), including Myh6, Myh7, Myh7b, Tnni3, Anp, Bnp, Gata4, Mef2c, Mef2d, Nfatc1, miR208a, and miR208b. In addition, DBcAMP altered the expression of DNA methyltransferases (Dnmts) and Tet methylcytosine dioxygenases (Tets), enzymes that regulate genomic DNA methylation levels. Changes in expression of DNA methylation genes induced by elevated cAMP led to increased global DNA methylation in HL-1 cells. In contrast, inhibition of DNMT activity with 5-azacytidine treatment decreased global DNA methylation levels and blocked the increased expression of several HCM genes (Myh7, Gata4, Mef2c, Nfatc1, Myh7b, Tnni3, and Bnp) observed with DBcAMP treatment. These results demonstrate that cAMP induces cardiomyocyte hypertrophy and altered HCM gene expression in vitro and that DNA methylation patterns mediate the upregulation of HCM genes induced by cAMP. These data identify a previously unknown mechanism by which elevated levels of cAMP lead to increased expression of genes associated with cardiomyocyte hypertrophy.

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Genome wide DNA methylation profiling for epigenetic alteration in coronary artery disease patients

Cited by 92 publications

References 52 publications

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

Epigenetic mechanisms in pulmonary arterial hypertension: the need for global perspectives

Association analysis between the distributions of histone modifications and gene expression in the human embryonic stem cell

cAMP induces hypertrophy and alters DNA methylation in HL-1 cardiomyocytes

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