• Title/Summary/Keyword: DNA-methylation

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DNA Methylation in Development (배아 발생에서의 DNA 메칠화)

  • Choe, Jin
    • Journal of Genetic Medicine
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    • v.5 no.2
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    • pp.100-104
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    • 2008
  • DNA methylation is one of many epigenetic mechanisms that regulate gene expression in the human body. From the view of epigenetics, there are two phases of development, one for germ cell development and another for embryo development. This review will discuss the basic mechanism of methylation, its role in gene expression, and the role of methylation in embryonic reprogramming. Methylation of genes is very critical to embryo development and should be explored further in order to increase our understanding of development.

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Effect of Body Mass Index on Global DNA Methylation in Healthy Korean Women

  • Na, Yeon Kyung;Hong, Hae Sook;Lee, Duk Hee;Lee, Won Kee;Kim, Dong Sun
    • Molecules and Cells
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    • v.37 no.6
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    • pp.467-472
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    • 2014
  • Obesity is known to be strongly associated with cardiovascular disease and cancer, the leading causes of mortality worldwide, and develops owing to interactions between genes and the environment. DNA methylation can act as a downstream effector of environmental signals, and analysis of this process therefore holds substantial promise for identifying mechanisms through which genetic and environmental factors jointly contribute to disease risk. Global DNA methylation of peripheral blood cells has recently been proposed as a potential biomarker for disease risk. Repetitive element DNA methylation has been shown to be associated with prominent obesity-related chronic diseases, but little is known about its relationship with weight status. In this study, we quantified the methylation of Alu elements in the peripheral blood DNA of 244 healthy women with a range of body mass indexes (BMIs) using pyrosequencing technology. Among the study participants, certain clinical laboratory parameters, including hemoglobin, serum glutamic oxaloacetic transaminase, serum glutamic- pyruvic transaminase, total cholesterol, and triglyceride levels were found to be strongly associated with BMI. Moreover, a U-shaped association between BMI and Alu methylation was observed, with the lowest methylation levels occurring at BMIs of between 23 and $30kg/m^2$. However, there was no significant association between Alu methylation and age, smoking status, or alcohol consumption. Overall, we identified a differential influence of BMI on global DNA methylation in healthy Korean women, indicating that BMI-related changes in Alu methylation might play a complex role in the etiology and pathogenesis of obesity. Further studies are required to elucidate the mechanisms underlying this relationship.

Alteration of DNA Methylation in Gastric Cancer with Chemotherapy

  • Choi, Su Jin;Jung, Seok Won;Huh, Sora;Chung, Yoon-Seok;Cho, Hyosun;Kang, Hyojeung
    • Journal of Microbiology and Biotechnology
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    • v.27 no.8
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    • pp.1367-1378
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    • 2017
  • Epigenetic alterations such as DNA methylation, histone acetylation, and chromatin remodeling can control gene expression by regulating gene transcription. DNA methylation is one of the frequent epigenetic events that play important roles in cancer development. Cancer cells can gain significant resistance to anticancer drugs and escape programmed cell death through major epigenetic changes, including DNA methylation. To date, several research groups have identified instances of both (i) hypermethylation of tumor suppressor genes, and (ii) global hypomethylation of oncogenes. These changes in DNA methylation status could be used as biomarkers for the diagnosis and prognosis of cancer patients undergoing chemotherapies or other clinical therapies. Herein, we describe genes for which methylation is dependent upon anticancer drug resistance in patients with gastric cancer; we then suggest a significant epigenetic target to focus on for overcoming anticancer drug resistance.

UNDERSTANDING OF EPIGENETICS AND DNA METHYLATION (후생유전학 (Epigenetics)과 DNA methylation의 이해)

  • Oh, Jung-Hwan;Kwon, Young-Dae;Yoon, Byung-Wook;Choi, Byung-Jun
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.30 no.3
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    • pp.302-309
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    • 2008
  • Epigenetic is usually referring to heritable traits that do not involve changes to the underlying DNA sequence. DNA methylation is known to serve as cellular memory. and is one of the most important mechanism of epigenetic. DNA methylation is a covalent modification in which the target molecules for methylation in mammalian DNA are cytosine bases in CpG dinucleotides. The 5' position of cytosine is methylated in a reaction catalyzed by DNA methyltransferases; DNMTl, DNMT3a, and DNMT3b. There are two different regions in the context of DNA methylation: CpG poor regions and CpG islands. The intergenic and the intronic region is considered to be CpG poor, and CpG islands are discrete CpG-rich regions which are often found in promoter regions. Normally, CpG poor regions are usually methylated whereas CpG islands are generally hypomethylated. DNA methylation is involved in various biological processes such as tissue-specific gene expression, genomic imprinting, and X chromosome inactivation. In general. cancer cells are characterized by global genomic hypomethylation and focal hypermethylation of CpG islands, which are generally unmethylated in normal cells. Gene silencing by CpG hypermethylation at the promotors of tumor suppressor genes is probably the most common mechanism of tumor suppressor inactivation in cancer.

Association of DNA Methylation Levels with Tissue-specific Expression of Adipogenic and Lipogenic Genes in Longissimus dorsi Muscle of Korean Cattle

  • Baik, M.;Vu, T.T.T.;Piao, M.Y.;Kang, H.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.27 no.10
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    • pp.1493-1498
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    • 2014
  • Epigenetic factors, such as DNA methylation status, may regulate adipogenesis and lipogenesis, thus affecting intramuscular fat (IMF) deposition in longissimus dorsi muscle (LM) of beef cattle. In Korean cattle steers, the LM consists mainly of muscle tissue. However, the LM tissue also contains IMF. We compared the gene expression levels between the IMF and muscle portions of the LM after tissue separation. Real-time polymerase chain reaction analysis showed that the mRNA levels of both adipogenic peroxisome proliferator-activated receptor gamma isoform 1 (PPARG1) and lipogenic fatty acid binding protein 4 (FABP4) were higher (p<0.01) in the IMF than in the muscle portion of the LM. We determined DNA methylation levels of regulatory regions of the PPARG1 and FABP4 genes by pyrosequencing of genomic DNA. DNA methylation levels of two of three CpG sites in the PPARG1 gene promoter region were lower (p<0.05) in the IMF than in the muscle portion of the LM. DNA methylation levels of all five CpG sites from the FABP4 gene promoter region were also lower (p<0.001) in the IMF than in the muscle portion. Thus, mRNA levels of both PPARG1 and FABP4 genes were inversely correlated with DNA methylation levels in regulatory regions of CpG sites of the corresponding gene. Our findings suggest that DNA methylation status regulates tissue-specific expression of adipogenic and lipogenic genes in the IMF and muscle portions of LM tissue in Korean cattle.

Folate and Homocysteine Levels during Pregnancy affect DNA Methylation in Human Placenta (임산부의 혈중 엽산과 호모시스틴 수준이 태반세포의 DNA 메틸화에 미치는 영향)

  • Park, Bo-Hyun;Kim, Young-Ju;Lee, Hwa-Young;Ha, Eun-Hee;Min, Jung-Won;Park, Jong-Soon;Park, Hye-Sook
    • Journal of Preventive Medicine and Public Health
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    • v.38 no.4
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    • pp.437-442
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    • 2005
  • Objectives : DNA methylation is one of the best characterized epigenetic mechanisms that play a regulatory role in genome programming and imprinting during embryogenesis. In this present study, we investigated the association between DNA methylation in the human placenta and the maternal folate and homocysteine concentrations on the Methylenetetrahydrofolatereductase (MTHFR) genetic polymorphism during pregnancy. Methods : We investigated 107 pregnant women who visited Ewha Woman's University Hospital for prenatal care during their $24{\sim}28$ weeks-period of gestation. During the second trimester, we measured the serum homocysteine and folate concentrations . The MTHFR 677 genetic polymorphism was determine by performing PCR-RFLP assay. The expression of DNA methylation in the human placentas was estimated by using immunohistochemistry method. Results : Serum folate was negatively correlated with the serum homocysteine concentration for all the MTHFR genotypes. We found positive correlation between the folate concentrations and the DNA methylation in the human placenta (p<0.05). An increasing concentration of homocysteine was associated with reduced DNA methylation in the human placenta. The coefficient value was -2.03 (-3.77, -0.29) on the regression model (p<0.05). Conclusion : These findings suggest that the maternal folate and homocysteine levels along with the MTHFR 677 genetic polymorphism during pregnancy affect the DNA methylation in the human placenta.

Methylation Patterns of Imprinting Genes, H19, Igf2r, and Snrpn, in Mouse Embryonic Stem Cells and Nuclear Transferred Embryonic Stem Cells (생쥐의 수정란 배아줄기세포와 체세포핵이식 배아줄기세포에서 각인유전자, H19, Igf2r, Snrpn의 메틸화 경향)

  • Lee, Min-Ho;Ju, Jin-Young;Cho, Youl-Hee;Shim, Sung-Han
    • Development and Reproduction
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    • v.14 no.4
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    • pp.253-259
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    • 2010
  • DNA methylation is one of the major epigenetic regulations of gene expression. The DNA methylation patterns are dramatically changed during gametogenesis and embryogenesis, and especially, it has been known that embryonic stem cells show a distinct methylation pattern. In this study, we examined the methylation patterns of imprinting genes, H19, Igf2r, and Snrpn, in stem cells induced from fertilized embryo (fES) and somatic cell nuclear transferred embryo (ntES). The methylation pattern of H19 gene in both fES and ntES were similar. However, the methylation patterns of Igf2r and Snrpn in ntES (hypermethylated) were slightly different from fES cells.

Modulation of DNA methylation by one-carbon metabolism: a milestone for healthy aging

  • Sang-Woon Choi ;Simonetta Friso
    • Nutrition Research and Practice
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    • v.17 no.4
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    • pp.597-615
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    • 2023
  • Healthy aging can be defined as an extended lifespan and health span. Nutrition has been regarded as an important factor in healthy aging, because nutrients, bioactive food components, and diets have demonstrated beneficial effects on aging hallmarks such as oxidative stress, mitochondrial function, apoptosis and autophagy, genomic stability, and immune function. Nutrition also plays a role in epigenetic regulation of gene expression, and DNA methylation is the most extensively investigated epigenetic phenomenon in aging. Interestingly, age-associated DNA methylation can be modulated by one-carbon metabolism or inhibition of DNA methyltransferases. One-carbon metabolism ultimately controls the balance between the universal methyl donor S-adenosylmethionine and the methyltransferase inhibitor S-adenosylhomocysteine. Water-soluble B-vitamins such as folate, vitamin B6, and vitamin B12 serve as coenzymes for multiple steps in one-carbon metabolism, whereas methionine, choline, betaine, and serine act as methyl donors. Thus, these one-carbon nutrients can modify age-associated DNA methylation and subsequently alter the age-associated physiologic and pathologic processes. We cannot elude aging per se but we may at least change age-associated DNA methylation, which could mitigate age-associated diseases and disorders.

Epigenetic Characterization of Aging Related Genes (노화 관련 유전자의 후성유전학적 특성 분석)

  • Ryu, Jea Woon;Lee, Sang Cheol;Yoo, Jaesoo;Kim, Hak Yong
    • The Journal of the Korea Contents Association
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    • v.13 no.8
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    • pp.466-473
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    • 2013
  • Gene expression is regulated by a wide range of mechanisms at the DNA sequence level. In addition, gene expression is also regulated by epigenetic mechanisms through DNA methylation, histone modification, and ncRNA. To understand the regulation of gene expression at the epigenetic level, we constructed aging related gene database and analyzed epigenetic properties that are focused on DNA methylation. The DNA methylation of promoter or upstream region of the genes induces to repress the gene expression. We compared and analyzed distribution between whole human genes and aging related genes in the epigenetic properties such as CGI distribution, methylation motif pattern, and TFBS (transcription factor binding site) distribution. In contrast to methylation motif pattern, CGI and TFBS distributions are positively correlated with epigenetic regulation of aging related gene expression. In this study, the epigenetic data about DNA methylation of the aging genes will provide us to understand phenomena of the aging and epigenetic mechanism for regulation of aging related genes.

Use of DNA Methylation for Cancer Detection and Molecular Classification

  • Zhu, Jingde;Yao, Xuebiao
    • BMB Reports
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    • v.40 no.2
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    • pp.135-141
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    • 2007
  • Conjugation of the methyl group at the fifth carbon of cytosines within the palindromic dinucleotide 5'-CpG-3' sequence (DNA methylation) is the best studied epigenetic mechanism, which acts together with other epigenetic entities: histone modification, chromatin remodeling and microRNAs to shape the chromatin structure of DNA according to its functional state. The cancer genome is frequently characterized by hypermethylation of specific genes concurrently with an overall decrease in the level of 5-methyl cytosine, the pathological implication of which to the cancerous state has been well established. While the latest genome-wide technologies have been applied to classify and interpret the epigenetic layer of gene regulation in the physiological and disease states, the epigenetic testing has also been seriously explored in clinical practice for early detection, refining tumor staging and predicting disease recurrence. This critique reviews the latest research findings on the use of DNA methylation in cancer diagnosis, prognosis and staging/classification.