• Title, Summary, Keyword: DNA methylation

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A lifelong exposure to a Western-style diet, but not aging, alters global DNA methylation in mouse colon

  • Choi, Sang-Woon;Tammen, Stephanie A;Liu, Zhenhua;Friso, Simonetta
    • Nutrition Research and Practice
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    • v.9 no.4
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    • pp.358-363
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    • 2015
  • BACKGROUND/OBJECTIVES: Previous studies have indicated that when compared to young mice, old mice have lower global DNA methylation and higher p16 promoter methylation in colonic mucosa, which is a common finding in colon cancer. It is also known that a Western-style diet (WSD) high in fat and calories, and low in calcium, vitamin D, fiber, methionine and choline (based on the AIN 76A diet) is tumorigenic in colons of mice. Because DNA methylation is modifiable by diet, we investigate whether a WSD disrupts DNA methylation patterns, creating a tumorigenic environment. SUBJECTVIES/METHODS: We investigated the effects of a WSD and aging on global and p16 promoter DNA methylation in the colon. Two month old male C57BL/6 mice were fed either a WSD or a control diet (AIN76A) for 6, 12 or 17 months. Global DNA methylation, p16 promoter methylation and p16 expression were determined by LC/MS, methyl-specific PCR and real time RT-PCR, respectively. RESULTS: The WSD group demonstrated significantly decreased global DNA methylation compared with the control at 17 months (4.05 vs 4.31%, P = 0.019). While both diets did not change global DNA methylation over time, mice fed the WSD had lower global methylation relative to controls when comparing all animals (4.13 vs 4.30%, P = 0.0005). There was an increase in p16 promoter methylation from 6 to 17 months in both diet groups (P < 0.05) but no differences were observed between diet groups. Expression of p16 increased with age in both control and WSD groups. CONCLUSIONS: In this model a WSD reduces global DNA methylation, whereas aging itself has no affect. Although the epigenetic effect of aging was not strong enough to alter global DNA methylation, changes in promoter-specific methylation and gene expression occurred with aging regardless of diet, demonstrating the complexity of epigenetic patterns.

DNA Methylation Biomarkers for Nasopharyngeal Carcinoma: Diagnostic and Prognostic Tools

  • Jiang, Wei;Cai, Rui;Chen, Qiu-Qiu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8059-8065
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    • 2016
  • Nasopharyngeal carcinoma (NPC) is a common tumor in southern China and south-eastern Asia. Effective strategies for the prevention or screening of NPC are limited. Exploring effective biomarkers for the early diagnosis and prognosis of NPC continues to be a rigorous challenge. Evidence is accumulating that DNA methylation alterations are involved in the initiation and progression of NPC. Over the past few decades, aberrant DNA methylation in single or multiple tumor suppressor genes (TSGs) in various biologic samples have been described in NPC, which potentially represents useful biomarkers. Recently, large-scale DNA methylation analysis by genome-wide methylation platform provides a new way to identify candidate DNA methylated markers of NPC. This review summarizes the published research on the diagnostic and prognostic potential biomarkers of DNA methylation for NPC and discusses the current knowledge on DNA methylation as a biomarker for the early detection and monitoring of progression of NPC.

Forensic DNA methylation profiling from evidence material for investigative leads

  • Lee, Hwan Young;Lee, Soong Deok;Shin, Kyoung-Jin
    • BMB Reports
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    • v.49 no.7
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    • pp.359-369
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    • 2016
  • DNA methylation is emerging as an attractive marker providing investigative leads to solve crimes in forensic genetics. The identification of body fluids that utilizes tissue-specific DNA methylation can contribute to solving crimes by predicting activity related to the evidence material. The age estimation based on DNA methylation is expected to reduce the number of potential suspects, when the DNA profile from the evidence does not match with any known person, including those stored in the forensic database. Moreover, the variation in DNA implicates environmental exposure, such as cigarette smoking and alcohol consumption, thereby suggesting the possibility to be used as a marker for predicting the lifestyle of potential suspect. In this review, we describe recent advances in our understanding of DNA methylation variations and the utility of DNA methylation as a forensic marker for advanced investigative leads from evidence materials.

Regulatory patterns of histone modifications to control the DNA methylation status at CpG islands

  • Jung, In-Kyung;Kim, Dong-Sup
    • Interdisciplinary Bio Central
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    • v.1 no.1
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    • pp.4.1-4.7
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    • 2009
  • Introduction: Histone modifications and DNA methylation are the major factors in epigenetic gene regulation. Especially, revealing how histone modifications are related to DNA methylation is one of the challenging problems in this field. In this paper, we address this issue and propose several plausible mechanisms for precise controlling of DNA methylation status at CpG islands. Materials and Methods: To establish the regulatory relationships, we used 38 histone modification types including H2A.Z and CTCF, and DNA methylation status at CpG islands across chromosome 6, 20, and 22 of human CD4+ T cell. We utilized Bayesian network to construct regulatory network. Results and Discussion: We found several meaningful relationships supported by previous studies. In addition, our results show that histone modifications can be clustered into several groups with different regulatory properties. Based on those findings we predicted the status of methylation level at CpG islands with high accuracy, and suggested core-regulatory network to control DNA methylation status.

Disappearance of Serum Methylated p16 Indicates Longer Survival in Patients with Gastric Cancer

  • Lim, Han-Ki;Park, Joong-Min;Chi, Kyong-Choun;Lee, Eun-Ju;Jeong, Eun-Mi
    • Journal of Gastric Cancer
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    • v.13 no.3
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    • pp.157-163
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    • 2013
  • Purpose: The aim of this study was to assess clinical correlations with postoperative alteration of p16 DNA methylation, and to clarify whether postoperative changes in the serum DNA methylation status of p16 could be used as a reliable prognostic factor for gastric cancer. Materials and Methods: Fifty-three consecutive gastric adenocarcinoma patients who underwent gastric resection (Chung-Ang University Hospital, Seoul, Korea) were included. DNA methylation of p16 was evaluated by methylation-specific polymerase chain reaction using serum DNA preoperatively and at the 10th postoperative day. The correlation between changes in methylation status and patients' prognosis was analyzed. Results: p16 was methylated in 79.2% of preoperative serum DNA and in 54.7% of postoperative serum DNA, respectively. Methylation in p16 disappeared more frequently in patients who underwent standard D2 lymphadenectomy compared to those who underwent modified D1+ lymphadenectomy (P=0.016). Whereas methylation of preoperative serum DNA was not correlated with survival, patients with postoperative disappearance of p16 methylation showed longer survival than those without postoperative disappearance of p16 methylation in the patients who had gastric cancer with lymph node metastasis (P=0.042). Conclusions: Postoperative disappearance of p16 methylation could be an available prognostic factor for node-positive gastric cancer.

DNA methylation-based age prediction from various tissues and body fluids

  • Jung, Sang-Eun;Shin, Kyoung-Jin;Lee, Hwan Young
    • BMB Reports
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    • v.50 no.11
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    • pp.546-553
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    • 2017
  • Aging is a natural and gradual process in human life. It is influenced by heredity, environment, lifestyle, and disease. DNA methylation varies with age, and the ability to predict the age of donor using DNA from evidence materials at a crime scene is of considerable value in forensic investigations. Recently, many studies have reported age prediction models based on DNA methylation from various tissues and body fluids. Those models seem to be very promising because of their high prediction accuracies. In this review, the changes of age-associated DNA methylation and the age prediction models for various tissues and body fluids were examined, and then the applicability of the DNA methylation-based age prediction method to the forensic investigations was discussed. This will improve the understandings about DNA methylation markers and their potential to be used as biomarkers in the forensic field, as well as the clinical field.

Analysis of sulphur and chlorine induced DNA cytosine methylation alterations in fresh corn (Zea mays L. saccharata and rugosa) leaf tissues by methylation sensitive amplification polymorphism (MSAP) approach

  • Zenda, Tinashe;Liu, Songtao;Yao, Daxuan;Duan, Huijun
    • Genes and Genomics
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    • v.40 no.9
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    • pp.913-925
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    • 2018
  • DNA (cytosine) methylation mechanism is another way through which plants respond to various cues including soil fertility amendments and abiotic stresses, and the mechanism has been used to infer some physiological, biochemical or adaptation processes. Despite numerous studies on global DNA methylation profiling in various crop species, however, researches on fresh corn (Zea mays L. saccharata or rugosa) remain largely unreported. The study aimed at investigating sulphur and chlorine induced DNA methylation changes in the fresh corn leaves of field-grown plants at the milk stage. Methylation sensitive amplification polymorphism (MSAP) technique was used to profile sulphur (S) and chlorine (Cl) induced DNA methylation patterns, levels and polymorphism alterations at the CCGG sites in fresh corn leaves of TDN21, JKN2000 and JKN928 hybrid cultivars. Twelve primer pairs used effectively detected 325 MSAP bands, exhibiting differentially methylated sites in the genomic DNA of all the three cultivars, with control showing higher (48.9-56.3%) type I bands as compared to sulphur (34.8-44.9%) and chlorine (40.9-47.4%) treatment samples. Consequently, total methylation levels were greater in S and Cl treatment samples than control; accounting for 43.7-59.7, 51.1-65.2 and 46.8-55.1% of total sites in TDN21, JKN2000 and JKN928, respectively. Full methylation of the internal cytosine was greater than hemi-methylation. Further, demethylation polymorphic loci significantly exceeded methylation polymorphic loci, being greater in S than Cl and control samples in all cultivars. Sulphur and chlorine have a profound influence on DNA methylation patterns and levels at the milk stage, principally by increasing the demethylation loci in the internal cytosine of the fresh corn genome. We speculate that these methylation alterations play an integral role in photosynthates assimilation and physiochemical pathways regulating quality parameters in kernels, as well as abiotic stress responses in fresh corn.

Changes in Polyamine Level and Chloroplast DNA Methylation in Chlamydomonas reinhardtii (Chlamydomonas의 Polyamine 함량변화와 엽록체 DNA Methylation)

  • 이순희
    • Journal of Plant Biology
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    • v.37 no.1
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    • pp.101-109
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    • 1994
  • Relationship between polyamine level and DNA methylation in the absence or presence of MGBG(l mM), which is an enzyme-activated reversible inhibitor of SAMDC, has been investigated during gametogenesis of Chlamydomonas. In the absence of MGBG, polyamine levels decreased in Chlamydomonas 137C(+) and 137C(-) during gametogenesis. And polyamine level of 137C(+) was 2-5 times as much as that of 137C(-) and showed a significant decrease unlike that of 137C(-). In vitro, MGBG inhibited ctDNA methylation of 137C(+) by 20-30% but did not inhibited that of 137C(-). Also, MGBG inhibited DNA methylase by 60% in vitro. The results obtained in the present work suggest the possibility that the changes of polyamine level may be associated with ctDNA methylation during gametogenesis of Chlamydomonas.omonas.

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DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese and Control Individuals

  • Rhee, Je-Keun;Lee, Jin-Hee;Yang, Hae Kyung;Kim, Tae-Min;Yoon, Kun-Ho
    • Genomics & Informatics
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    • v.15 no.1
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    • pp.28-37
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    • 2017
  • Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls. We observed that the hierarchical clustering of DNA methylation, but not gene expression, clearly segregates the obese individuals from the controls, suggesting that the metabolic disturbance that occurs as a result of obesity at a young age may affect the DNA methylation of peripheral blood cells without accompanying transcriptional changes. To examine the genome-wide differences in the DNA methylation profiles of young obese and control individuals, we identified differentially methylated CpG sites and investigated their genomic and epigenomic contexts. The aberrant DNA methylation patterns in obese individuals can be summarized as relative gains and losses of DNA methylation in gene promoters and gene bodies, respectively. We also observed that the CpG islands of obese individuals are more susceptible to DNA methylation compared to controls. Our pilot study suggests that the genome-wide aberrant DNA methylation patterns of obese individuals may advance not only our understanding of the epigenomic pathogenesis but also early screening of obesity in youth.

A Visualization Tool for Computational Analysis of DNA Methylation Level Using Bisulfite Sequencing Data

  • Tae, Hong-Seok
    • Genomics & Informatics
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    • v.9 no.3
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    • pp.136-137
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    • 2011
  • Methylation of cytosine is a post-synthesis modification that does not affect the primary DNA sequence but greatly influences gene expression level and phenotypes of an organism. As high-throughput sequencing of bisulfite-treated DNA is the most efficient method to identify methylated sites, several tools to map sequencing reads on a reference are available. But tools to visualize and to interpret the methylation level of methylation sites are currently insufficient. Herein, we present a novel tool to visualize the methylation level of CpG sites.