Genome-wide analysis of DNA methylation in pigs using reduced representation bisulfite sequencing

Choi, Mi Hyun; Lee, Jongin; Lee, Wang Jae; Nguyen, Dinh-Truong; Park, Suhyun; Soundrarajan, Nagasundarapandian; Schachtschneider, Kyle M.; Kim, Jaebum; Park, Jin-Ki; Kim, Jin‐Hoi; Park, Chankyu

doi:10.1093/dnares/dsv017

Cited by 53 publications

(62 citation statements)

References 72 publications

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“…1A). These findings were in concordance with previous reports regarding pigs394344. CpG islands (CpGi) showed significantly reduced methylation in comparison with that of CpGi shores or CpGi shelfs (Fig.…”

Section: Resultssupporting

confidence: 93%

“…Hypermethylation is generally abolished during myogenic terminal differentiation and hypomethylation has very strong associations with genes related to contractile fiber38. Several studies have been performed to explore the genome-wide methylation profiling in pig muscle and other tissues using reduced representation bisulfite sequencing (RRBS)3940 or methylated DNA immunoprecipitation sequencing (MeDIP-seq) methods4142. Jin et al .…”

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confidence: 99%

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Comparative analysis of DNA methylome and transcriptome of skeletal muscle in lean-, obese-, and mini-type pigs

Yang

Liang

Niu

et al. 2017

Sci Rep

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DNA methylation plays a pivotal role in biological processes by affecting gene expression. However, how DNA methylation mediates phenotype difference of skeletal muscle between lean-, obese-, and mini-type pigs remains unclear. We systematically carried out comparative analysis of skeletal muscle by integrating analysis of genome-wide DNA methylation, mRNA, lncRNA and miRNA profiles in three different pig breeds (obese-type Tongcheng, lean-type Landrace, and mini-type Wuzhishan pigs). We found that the differentially methylated genes (DMGs) were significantly associated with lipid metabolism, oxidative stress and muscle development. Among the identified DMGs, 253 genes were related to body-size and obesity. A set of lncRNAs and mRNAs including UCP3, FHL1, ANK1, HDAC4, and HDAC5 exhibited inversely changed DNA methylation and expression level; these genes were associated with oxidation reduction, fatty acid metabolism and cell proliferation. Gene regulatory networks involved in phenotypic variation of skeletal muscle were related to lipid metabolism, cellular movement, skeletal muscle development, and the p38 MAPK signaling pathway. DNA methylation potentially influences the propensity for obesity and body size by affecting gene expression in skeletal muscle. Our findings provide an abundant information of epigenome and transcriptome that will be useful for animal breeding and biomedical research.

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Section: Resultssupporting

confidence: 93%

mentioning

confidence: 99%

Comparative analysis of DNA methylome and transcriptome of skeletal muscle in lean-, obese-, and mini-type pigs

Yang

Liang

Niu

et al. 2017

Sci Rep

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“…Despite recent studies using patient samples 15–18 and pigs, 28, 29 the molecular mechanisms for how altered DNA methylation contributes to the progression of cardiomyopathy remains unclear. Such clinical studies are important to demonstrate the involvement of DNA methylation in cardiovascular disease, yet are limited due to the genetic, environmental and disease heterogeneity of human samples.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States

Chen

Orozco

Wang

et al. 2016

Circulation Research

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Rationale Only a small portion of the known heritability of cardiovascular diseases such as heart failure can be explained based on single gene mutations. Chromatin structure and regulation provide a substrate through which genetic differences in non-coding regions may impact cellular function and response to disease, but the mechanisms are unknown. Objective We conducted genome-wide measurements of DNA methylation in different strains of mice that are susceptible and resistant to isoproterenol-induced dysfunction to test the hypothesis that this epigenetic mark may play a causal role in the development of heart failure. Methods and Results BALB/cJ and BUB/BnJ mice, determined to be susceptible and resistant to isoproterenol-induced heart failure respectively, were administered the drug for 3 weeks via osmotic minipump. Reduced representational bisulfite sequencing was then used to compare the differences between the cardiac DNA methylome in the basal state between strains and then following isoproterenol treatment. Single base resolution DNA methylation measurements were obtained and revealed a bimodal distribution of methylation in the heart, enriched in lone intergenic CpGs and depleted from CpG islands around genes. Isoproterenol induced global decreases in methylation in both strains; however, the basal methylation pattern between strains shows striking differences that may be predictive of disease progression prior to environmental stress. The global correlation between promoter methylation and gene expression (as measured by microarray) was modest and revealed itself only with focused analyses of transcription start site and gene body regions (in contrast to when gene methylation was examined in toto). Modules of co-methylated genes displayed correlation with other protein-based epigenetic marks supporting the hypothesis that chromatin modifications act in a combinatorial manner to specify transcriptional phenotypes in the heart. Conclusions This study provides the first single base-resolution map of the mammalian cardiac DNA methylome and the first case-control analysis of the changes in DNA methylation with heart failure. The findings demonstrate marked genetic differences in DNA methylation that are associated with disease progression.

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“…[144][145][146] The advancement in using porcine models is due to the high degree of homology in anatomy, physiology, size, cell biology, key metabolizing enzymes, genetics, and epigenetics between pigs and humans. [147][148][149][150][151][152][153][154][155][156][157] In addition, the life-span of the pig also offers an opportunity to monitor and characterize disease development and progression over a human-relevant amount of time. 36,149,158 Importantly for cancer research, porcine somatic cells, consistent with human cells, suppress telomerase activity in most tissues, which is then reactivated during tumorigenesis.…”

Section: Porcine Models Of Immuno-oncologymentioning

confidence: 99%

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

et al. 2018

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The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E’s, is encompassed by 3 distinct phases of elimination, equilibrium, and escape. Despite impressive results in the clinic, cancer immunotherapy still has room for improvement as many patients remain unresponsive to therapy. Moreover, many of the preclinical results obtained in the widely used mouse models of cancer are lost in translation to human patients. To improve the success rate of immuno-oncology research and preclinical testing of immune-based anticancer therapies, using alternative animal models more closely related to humans is a promising approach. Here, we describe 2 of the major alternative model systems: canine (spontaneous) and porcine (experimental) cancer models. Although dogs display a high rate of spontaneous tumor formation, an increased number of genetically modified porcine models exist. We suggest that the optimal immuno-oncology model may depend on the stage of cancer immunoediting in question. In particular, the spontaneous canine tumor models provide a unique platform for evaluating therapies aimed at the escape phase of cancer, while genetically engineered swine allow for elucidation of tumor-immune cell interactions especially during the phases of elimination and equilibrium.

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Genome-wide analysis of DNA methylation in pigs using reduced representation bisulfite sequencing

Cited by 53 publications

References 72 publications

Comparative analysis of DNA methylome and transcriptome of skeletal muscle in lean-, obese-, and mini-type pigs

Comparative analysis of DNA methylome and transcriptome of skeletal muscle in lean-, obese-, and mini-type pigs

DNA Methylation Indicates Susceptibility to Isoproterenol-Induced Cardiac Pathology and Is Associated With Chromatin States

Of Mice, Dogs, Pigs, and Men: Choosing the Appropriate Model for Immuno-Oncology Research

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