• Genes and Genomics
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• 제40권12호
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• pp.1363-1371
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• 2018

One of the main concerns in biology is extracting sophisticated features from DNA sequence for gene interaction determination, receiving a great deal of researchers' attention. The epigenetic modifications along with their patterns have been intensely recognized as dominant features affecting on gene expression. However, studying sequenced-based features highly correlated to this key element has remained limited. The main objective in this research was to propose a new feature highly correlated to epigenetic modifications capable of classification of genes. In this paper, classification of 34 genes in PPAR signaling pathway associated with muscle fat tissue in human was performed. Using different statistical outlier detection methods, we proposed that 5-mers highly correlated to epigenetic modifications can correctly categorize the genes involved in the same biological pathway or process. Thirty-four genes in PPAR signaling pathway were classified via applying a proposed feature, 5-mers strongly associated to 17 different epigenetic modifications. For this, diverse statistical outlier detection methods were applied to specify the group of thoroughly correlated genes. The results indicated that these 5-mers can appropriately identify correlated genes. In addition, our results corresponded to GeneMania interaction information, leading to support the suggested method. The appealing findings imply that not only epigenetic modifications but also their highly correlated 5-mers can be applied for reconstructing gene regulatory networks as supplementary data as well as other applications like physical interaction, genes prioritization, indicating some sort of data fusion in this analysis.

• 생명과학회지
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• 제33권9호
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• pp.736-745
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• 2023

노화란 세포 및 생리 기능이 점진적으로 손상되는 복잡한 과정이다. 알츠하이머, 동맥경화 및 갱년기와 같은 노화와 관련된 질병은 노화가 진행이 되면서 발생된다. 노화와 관련된 질환은 다양한 원인에 의해 발생된다. 그 중 유전적인 변화 없이 유전자 발현을 조절하는 후성유전의 변화는 노화, 그리고 노화와 관련된 질환의 발생에 중요한 조절자로 알려져있다. 이 리뷰에서는 후성유전의 변화가 노화 및 노화와 관련된 질병의 발전과 진행에 어떠한 역할을 하는지에 대해 서술하였다. 노화 중에 일어나는 유전적 변화의 분자적 기전과 이러한 변화가 노화와 관련된 질병에 미치는 영향, 특히 노화와 관련된 질환과 관련된 유전자 발현 양식을 조절하는 RNA 메틸화, DNA 메틸화 및 miRNA에 대해 중점적으로 초점을 맞추었다.

• Parasites, Hosts and Diseases
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• 제62권1호
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• pp.98-116
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• 2024

Epigenetic writers including DNA and histone lysine methyltransferases (DNMT and HKMT, respectively) play an initiative role in the differentiation and development of eukaryotic organisms through the spatiotemporal regulation of functional gene expressions. However, the epigenetic mechanisms have long been suspected in helminth parasites lacking the major DNA methyltransferases DNMT1 and DNMT3a/3b. Very little information on the evolutionary status of the epigenetic tools and their role in regulating chromosomal genes is currently available in the parasitic trematodes. We previously suggested the probable role of a DNMT2-like protein (CsDNMT2) as a genuine epigenetic writer in a trematode parasite Clonorchis sinensis. Here, we analyzed the phylogeny of HKMT subfamily members in the liver fluke and other platyhelminth species. The platyhelminth genomes examined conserved genes for the most of SET domain-containing HKMT and Disruptor of Telomeric Silencing 1 subfamilies, while some genes were expanded specifically in certain platyhelminth genomes. Related to the high gene dosages for HKMT activities covering differential but somewhat overlapping substrate specificities, variously methylated histones were recognized throughout the tissues/organs of C. sinensis adults. The temporal expressions of genes involved in eggshell formation were gradually decreased to their lowest levels proportionally to aging, whereas those of some epigenetic tool genes were re-boosted in the later adult stages of the parasite. Furthermore, these expression levels were significantly affected by treatment with DNMT and HKMT inhibitors. Our data strongly suggest that methylated histones are potent epigenetic markers that modulate the spatiotemporal expressions of C. sinensis genes, especially those involved in sexual reproduction.

• Current Research on Agriculture and Life Sciences
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• 제28권
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• pp.63-68
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• 2010

The epigenetic therapy of cancers is emerging as an effective and valuable approach to both chemotherapy and the chemoprevention of cancer. The utilization of epigenetic targets that include histone methyltransferase (HMTase), Histone deacetylatase, and DNA methyltransferase, are emerging as key therapeutic targets. SET containing proteins such as the HMTase Setd1b has been found significantly amplified in cancerous cells. In order to shed some light on the histone methyl transferase family, we cloned the Setd1b gene from Mus musculus and build a collection of vectors for recombinant protein expression in E.coli that will pave the way for further structural biology studies. We prospect the role of the Setd1b pathway in cancer therapy and detail its unique value for designing novel anti-cancer epigenetic-drugs.

• 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.

• 한국균학회소식:학술대회논문집
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• 한국균학회 2018년도 춘계학술대회 및 임시총회
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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.

• Restorative Dentistry and Endodontics
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• 제40권1호
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• pp.14-22
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• 2015

Genetic information such as DNA sequences has been limited to fully explain mechanisms of gene regulation and disease process. Epigenetic mechanisms, which include DNA methylation, histone modification and non-coding RNAs, can regulate gene expression and affect progression of disease. Although studies focused on epigenetics are being actively investigated in the field of medicine and biology, epigenetics in dental research is at the early stages. However, studies on epigenetics in dentistry deserve attention because epigenetic mechanisms play important roles in gene expression during tooth development and may affect oral diseases. In addition, understanding of epigenetic alteration is important for developing new therapeutic methods. This review article aims to outline the general features of epigenetic mechanisms and describe its future implications in the field of dentistry.

• Journal of Plant Biotechnology
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• 제44권1호
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• pp.19-26
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• 2017

Rapid progress in epigenetic studies has resulted in genome wide information of genetic functions, other than DNA sequence information. However, insufficient understanding and unclear research direction in epigenetics has failed to attract many researchers. Here, we review the sexual reproduction processes that are particularly related to epigenetics in plants. We aim to elucidate the roles of epigenetic information and molecular mechanisms involved in the complex sexual reproduction process of plants, and examine their biological significance.

• Toxicological Research
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• 제33권1호
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• pp.1-5
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• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• Genomics & Informatics
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• 제15권4호
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• pp.170-177
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• 2017

HOTAIR is an lncRNA that has been known to have an oncogenic role in different cancers. There is limited knowledge of genetic and epigenetic elements and their interactions for the gene encoding HOTAIR. Therefore, understanding the molecular mechanism and its regulation remains to be challenging. We used different in silico analyses to find genetic and epigenetic elements of HOTAIR gene to gain insight into its regulation. We reported different regulatory elements including canonical promoters, transcription start sites, CpGIs as well as epigenetic marks that are potentially involved in the regulation of HOTAIR gene expression. We identified repeat sequences and single nucleotide polymorphisms that are located within or next to the CpGIs of HOTAIR. Our analyses may help to find potential interactions between genetic and epigenetic elements of HOTAIR gene in the human tissues and show opportunities and limitations for researches on HOTAIR gene in future studies.