• Nutrition Research and Practice
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• 제17권1호
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• pp.13-31
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• 2023

BACKGROUND/OBJECTIVES: Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed. MATERIALS/METHODS: Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated. RESULTS: Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity. CONCLUSIONS: Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

• BMB Reports
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• 제40권2호
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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.

• Parasites, Hosts and Diseases
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• 제54권2호
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• pp.133-138
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• 2016

Encystation is an essential process for Acanthamoeba survival under nutrient-limiting conditions and exposure to drugs. The expression of several genes has been observed to increase or decrease during encystation. Epigenetic processes involved in regulation of gene expression have been shown to play a role in several pathogenic parasites. In the present study, we identified the protein arginine methyltransferase 5 (PRMT5), a known epigenetic regulator, in Acanthamoeba castellanii. PRMT5 of A. castellanii (AcPRMT5) contained domains found in S-adenosylmethionine-dependent methyltransferases and in PRMT5 arginine-N-methyltransferase. Expression levels of AcPRMT5 were increased during encystation of A. castellanii. The EGFP-PRMT5 fusion protein was mainly localized in the nucleus of trophozoites. A. castellanii transfected with siRNA designed against AcPRMT5 failed to form mature cysts. The findings of this study lead to a better understanding of epigenetic mechanisms behind the regulation of encystation in cyst-forming pathogenic protozoa.

• Asian-Australasian Journal of Animal Sciences
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• 제27권11호
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• pp.1532-1539
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• 2014

Although growth rate is one of the main economic traits of concern in pig production, there is limited knowledge on its epigenetic regulation, such as DNA methylation. In this study, we conducted methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) to compare genome-wide DNA methylation profile of small intestine and liver tissue between fast- and slow-growing weaning piglets. The genome-wide methylation pattern between the two different growing groups showed similar proportion of CpG (regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence) coverage, genomic regions, and gene regions. Differentially methylated regions and genes were also identified for downstream analysis. In canonical pathway analysis using differentially methylated genes, pathways (triacylglycerol pathway, some cell cycle related pathways, and insulin receptor signaling pathway) expected to be related to growth rate were enriched in the two organ tissues. Differentially methylated genes were also organized in gene networks related to the cellular development, growth, and carbohydrate metabolism. Even though further study is required, the result of this study may contribute to the understanding of epigenetic regulation in pig growth.

• BMB Reports
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• 제49권10호
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• pp.578-583
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• 2016

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.

• 생물정신의학
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• 제18권4호
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• pp.181-188
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• 2011

Major depression is a devastating disorder of which lifetime prevalence rate is as high as up to 25% in general population. Although the etiology of the disorder is still poorly understood, it is generally accepted that both genetic and environmental factors are involved in the precipitation of depression. Stressful lifetime events are potent precipitating environmental factors for major depression and early-life stress is in particular an important element that predisposes individuals to major depression later in life. How environmental factors such as stress can make our neural networks susceptible to depression and how those factors leave long-lasting influences have been among the major questions in the field of depression research. Epigenetic regulations can provide a bridging mechanism between environmental factors and genetic factors so that these two factors can additively determine individual predispositions to major depression. Here we introduce epigenetic regulations as candidate mechanisms that mediate the integration of environmental adversaries with genetic predispositions, which may lead to the development of major depression, and summarize basic molecular events that underlie epigenetic regulations as well as experimental evidences that support the active role of epigenetic regulation in major depression.

• Journal of Microbiology and Biotechnology
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• 제28권2호
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• pp.181-189
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• 2018

Candida albicans is a major pathogenic fungus in humans, and meets at first the innate immune cells, such as macrophages, in its host. One important strategy of the host cell to kill C. albicans is to produce reactive oxygen species (ROS) by the macrophages. In response to ROS produced by the macrophages, C. albicans operates its defense mechanisms against them by expressing its oxidative stress response genes. Although there have been many research studies explaining the specific transcription factors and the expression of the oxidative stress genes in C. albicans, the regulation of the oxidative stress genes by chromatin structure is little known. Epigenetic regulation by the chromatin structure is very important for the regulation of eukaryotic gene expression, including the chromatin structure dynamics by histone modifications. Among various histone modifications, histone acetylation is reported for its direct relationship to the regulation of gene expression. Recent studies reported that histone acetyltransferases regulate genes to respond to the oxidative stress in C. albicans. In this review, we introduce all histone acetyltransferases that C. albicans contains and some papers that explain how histone acetyltransferases participate in the oxidative stress response in C. albicans.

• Animal cells and systems
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• 제12권3호
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• pp.117-125
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• 2008

One of the interesting trends in genome research is the study about epigenetic modification above single gene level. Epigenetics refers study about heritable change in the genome, which accompany modification in DNA or Chromatin besides DNA sequence alteration. We used to have the idea that the coding potential of the genome lies within the arrangement of the four bases A, T, G, C; However, additional information that affects phenotype is stored in the distribution of the modified base 5-methylcytosine. This form of information storage is flexible enough to be adapted for different somatic cell types, yet is stable enough to be retained during mitosis and/or meiosis. Epigenetic modification is a modification of the genome, as opposed to being part of the genome, so is known as "epigenetics"(Greek for "upon" genetics). This modification could be methylation on Cytosine base or post translational modification on histone protein(methylation, acetylation, phosphorylation, Sumoylation)($Dimitrijevi\hat{E}$ et al 2005). In this review, we would like to focus on the relationship of DNA methylation and cancer.

• Korean Circulation Journal
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• 제53권6호
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• pp.404-405
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• 2023

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6433-6438
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• 2013

In hepatocellular cancer (HCC), lack of response to chemotherapy and radiation treatment can be caused by a loss of epigenetic modifications of cancer cells. Methionine adenosyltransferase 1A is inactivated in HCC and may be stimulated by an epigenetic change involving promoter hypermethylation. Therefore, drugs releasing epigenetic repression have been proposed to reverse this process. We studied the effect of the demethylating reagent 5-aza-2'-deoxycitidine (5-Aza-CdR) on MAT1A gene expression, DNA methylation and S-adenosylmethionine (SAMe) production in the HCC cell line Huh7. We found that MAT1A mRNA and protein expression were activated in Huh7 cells with the treatment of 5-Aza-CdR; the status of promoter hypermethylation was reversed. At the same time, MAT2A mRNA and protein expression was significantly reduced in Huh7 cells treated with 5-Aza-CdR, while SAMe production was significantly induced. However, 5-Aza-CdR showed no effects on MAT2A methylation. Furthermore, 5-Aza-CdR inhibited the growth of Huh7 cells and induced apoptosis and through down-regulation of Bcl-2, up-regulation of Bax and caspase-3. Our observations suggest that 5-Aza-CdR exerts its anti-tumor effects in Huh7 cells through an epigenetic change involving increased expression of the methionine adenosyltransferase 1A gene and induction of S-adenosylmethionine production.