• Molecules and Cells
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• v.41 no.4
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• pp.264-270
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• 2018

Cells cope with diverse intrinsic and extrinsic stimuli in order to make adaptations for survival. The epigenetic landscape plays a crucial role in cellular adaptation, as it integrates the information generated from stimuli. Signaling pathways induced by stimuli communicate with chromatin to change the epigenetic landscape through regulation of epigenetic modifiers. Metabolic dynamics altered by these stimuli also affect the activity of epigenetic modifiers. Here, I review the current understanding of epigenetic regulation via signaling and metabolic pathways. In addition, I will discuss possible ways to achieve specificity of epigenetic modifications through the cooperation of stimuli-induced signal transduction and metabolic reprogramming.

• Korean Journal of Biological Psychiatry
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• v.15 no.4
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• pp.243-253
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• 2008

In the post-genomic era, the mechanisms controlling activation of genes are thought to be more important. Gene-environment interactions are crucial in both development and treatment of psychiatric disorders as they are complex genetic disorders. Epigenetics is defined as a change of gene expression that occurs without a change of DNA sequence and can be heritable by certain mechanisms. Epigenetic changes play essential roles in control of gene activation. DNA methylation, chromatin remodeling and RNAi act as key mechanisms for epigenetic modifications of genes. Here, we review the basic mechanisms of epigenetics and discuss their potential involvement of human diseases, including psychiatric disorders.

• Genomics & Informatics
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• v.17 no.3
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• pp.24.1-24.8
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• 2019

Early environmental exposure is recognized as a key factor for long-term health based on the Developmental Origins of Health and Disease hypothesis. It considers that early-life nutrition is now being recognized as a major contributor that may permanently program change of organ structure and function toward the development of diseases, in which epigenetic mechanisms are involved. Recent researches indicate early-life environmental factors modulate the microbiome development and the microbiome might be mediate diet-epigenetic interaction. This review aims to define which nutrients involve microbiome development during the critical window of susceptibility to disease, and how microbiome modulation regulates epigenetic changes and influences human health and future prevention strategies.

• 한국균학회소식:학술대회논문집
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• 2018.05a
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• pp.19-19
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• 2018

Fungal pathogens have huge impact on health and economic wellbeing of human by causing life-threatening mycoses in immune-compromised patients or by destroying crop plants. A key determinant of fungal pathogenesis is their ability to undergo developmental change in response to host or environmental factors. Genetic pathways that regulate such morphological transitions and adaptation are therefore extensively studied during the last few decades. Given that epigenetic as well as genetic components play pivotal roles in development of plants and mammals, contribution of microbial epigenetic counterparts to this morphogenetic process is intriguing yet nearly unappreciated question to date. To bridge this gap in our knowledge, we set out to investigate histone modifications among epigenetic mechanisms that possibly regulate fungal adaptation and processes involved in pathogenesis of a model plant pathogenic fungus, Magnaporthe oryzae. For functional and comparative analysis of histone modifications, a web-based database (dbHiMo) was constructed first to archive and analyze histone modifying enzymes from eukaryotic species whose genome sequences are available. Based on the database entries, we carried out functional analysis of genes encoding histone modifying enzymes. Here I provide examples of such analyses that show how histone acetylation and methylation is implicated in regulating important aspects of fungal pathogenesis. Current analysis of histone modifying enzymes is followed by ChIP-seq and RNA-seq experiments to pinpoint the genes that are controlled by particular histone modifications. We anticipate that our work will provide not only the significant advances in our understanding of epigenetic mechanisms operating in microbial eukaryotes but also basis to expand our perspective on regulation of development in fungal pathogens.

• Journal of Life Science
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• v.33 no.9
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• pp.736-745
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• 2023

Aging is a complex biological process characterized by a gradual decline in cellular and physiological functions. This natural process is associated with age-related diseases, including Alzheimer's disease, atherosclerosis, and hypogonadism, which are significant health concerns among older individuals and can significantly impact their quality of life. Researchers have found that epigenetic markers play a crucial role in regulating aging and age-related diseases. Epigenetic markers are heritable gene expression alterations that do not change in the DNA sequence. This review focuses on the involvement of various epigenetic marks, such as RNA methylation, DNA methylation, and microRNAs (miRNAs), in regulating gene expression patterns associated with age-related diseases, such as Alzheimer's disease, atherosclerosis, and hypogonadism. These epigenetic alterations can lead to the dysregulation of specific genes and signaling pathways, contributing to the development and progression of Alzheimer's disease, atherosclerosis, and hypogonadism. Understanding the molecular mechanisms behind these epigenetic modifications is essential for both the aging population and individuals seeking ways to promote overall well-being. By gaining deeper insights into how epigenetic marker alteration occurs during aging and age-related diseases, researchers can potentially develop targeted therapeutic strategies to alleviate the impact of these conditions and improve the quality of life for older individuals.

• Journal of Environmental Health Sciences
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• v.35 no.5
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• pp.343-354
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• 2009

Since Barker found associations between low birth weight and several chronic diseases later in life, the hypothesis of fetal origins of adult disease (aka, Barker Hypothesis) and epigenetics have been emerging as a new paradigm for geneenvironment interaction of chronic disease. Epigenetics is the study of heritable changes in gene silencing that occur without any change in DNA sequence. Gene expression can be regulated by several epigenetic mechanisms, including DNA methylation and histone modifications, which may be associated with chronic conditions, such as cancers, cardiovascular disease, and type-2 diabetes. One carbon metabolism which involves the transfer of a methyl group catalyzed by DNA methyltransferase is an important mechanism by which DNA methylation occurs in promoter regions and/or repetitive elements of the genome. Environmental factors may induce epigenetic modification through production of reactive oxygen species, alteration of methyltransferase activity, and/or interference with methyl donors. In this review, we introduce recent studies of epigenetic modification and environmental factors, such as heavy metals, environmental hormones, air pollution, diet and psychosocial stress. We also discuss epigenetic perspectives of early life environmental exposure and late life disease occurrence.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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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.

• Proceedings of the Korean Society of Food Science and Nutrition Conference
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• 2004.11a
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• pp.271-274
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• 2004

Nutritional genomics is a new field of study of how nutrition interacts with an individual's genome or individual responds to individual diets. Systematic approach of nutritional genomics will likely provide important clues about responders and non-responders. The current interest in personalizing health stems from the breakthroughs emerging in integrative technologies of genomics and epigenomics and the identification of genetic and epigentic diversity in individual's genetic make-up that are associated with variations in many aspects of health, including diet-related diseases. Microarray is a powerful screen system that is being also currently employed in nutritional research. Monitoring of gene expression at genome level is now possible with this technology, which allows the simultaneous assessment of the transcription of tens of thousands of genes and of their relative expression of pathological cells such tumor cells compared with that of normal cells. Epigenetic events such as DNA methylation can result in change of gene expression without involving changes in gene sequence. Recent developed technology of DNAarray-based methylation assay will facilitate wide study of epigenetic process in nutrigenomics. Some of the areas that would benefitfrom these technologies include identifying molecular targets (Biomarkers) for the risk and benefit assessment. These characterized biomarkers can reflect expose, response, and susceptibility to foods and their components. Furthermore the identified new biomarker perhaps can be utilized as a indicator of delivery system fur optimizing health.

• Genomics & Informatics
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• v.11 no.4
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• pp.164-173
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• 2013

Genomic instability, which occurs through both genetic mechanisms (underlying inheritable phenotypic variations caused by DNA sequence-dependent alterations, such as mutation, deletion, insertion, inversion, translocation, and chromosomal aneuploidy) and epigenomic aberrations (underlying inheritable phenotypic variations caused by DNA sequence-independent alterations caused by a change of chromatin structure, such as DNA methylation and histone modifications), is known to promote tumorigenesis and tumor progression. Mechanisms involve both genomic instability and epigenomic aberrations that lose or gain the function of genes that impinge on tumor suppression/prevention or oncogenesis. Growing evidence points to an epigenome-wide disruption that involves large-scale DNA hypomethylation but specific hyper-methylation of tumor suppressor genes, large blocks of aberrant histone modifications, and abnormal miRNA expression profile. Emerging molecular details regarding the modulation of these epigenetic events in cancer are used to illustrate the alterations of epigenetic molecules, and their consequent malfunctions could contribute to cancer biology. More recently, intriguing evidence supporting that genetic and epigenetic mechanisms are not separate events in cancer has been emerging; they intertwine and take advantage of each other during tumorigenesis. In addition, we discuss the collusion between epigenetics and genetics mediated by heterochromatin protein 1, a major component of heterochromatin, in order to maintain genome integrity.

• BMB Reports
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• v.51 no.5
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• pp.211-218
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• 2018

Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation. Although the underlying mechanisms suggesting how histone cleavage affects gene expression in view of chromatin structure are only beginning to be understood, it is clear that this process is a novel transcriptional epigenetic mechanism involving chromatin dynamics. In this review, we describe the functional properties of the known histone tail cleavage with its proteolytic enzymes, discuss how histone cleavage impacts gene expression, and present future directions for this area of study.