• Title/Summary/Keyword: 후성유전학

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Epigenomic Control System for Cancer-Related Genes Based on Network (네트워크 기반 암 관련 유전자의 후성유전학적 제어 시스템)

  • Kim, Hak Yong
    • Proceedings of the Korea Contents Association Conference
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    • 2012.05a
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    • pp.169.2-169.2
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    • 2012
  • 암 관련 유전자를 후성유전학적으로 제어하는 방법에는 miRNA, DNA 메틸화, 그리고 히스톤 단백질의 변형에 의해서 가능하다. 그러나 후성유전학적 방법을 통해서 암 관련 유전자를 제어하기 위해서는 첫째, 한 유전자에 여러 miRNA들에 의해서 조절되기 때문에 선택의 문제가 있으며, 둘째, 암 관련 유전자를 제어하는 DNA 메틸화 패턴이 다양하며, 셋째, 히스톤 단백질의 변형 자체가 다양하며 각 유전자에 대한 히스톤 변형의 특이성이 있다. 따라서 후성유전학 기반 하에서 암 관련 유전자를 제어하기 위해서는 시스템 수준에서의 접근이 바람직하다. 본 연구에서는 암 관련 유전자의 네트워크를 구축하고, 이 네트워크를 기반으로 암 유전자를 제어하는 miRNA에 최우선 순위를 부여하는 방법, 암 유전자의 DNA 메틸화 모티프 패턴을 분석하는 방법, 히스톤 변형과 암 관련유전자의 상관관계를 분석하는 방법을 제시하고자 한다.

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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.

Epigenetic Mechanisms of Depression: Role of Histone Modification and DNA Methylation in BDNF Gene (우울증의 후성유전기전: BDNF 유전자의 히스톤 변형 및 DNA 메틸화의 역할)

  • Park, Sung Woo
    • Journal of Life Science
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    • v.28 no.12
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    • pp.1536-1544
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    • 2018
  • Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

Evolutionary association learning for detecting higher-order interactions of DNA methylation regions in human diseases (인간 질병에서 DNA 메틸화 지역의 고차상호작용 탐색을 위한 진화적 연관관계 학습)

  • Rhee, Je-Keun;Kim, Soo-Jin;Zhang, Byoung-Tak
    • Proceedings of the Korean Information Science Society Conference
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    • 2012.06b
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    • pp.420-422
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    • 2012
  • DNA 메틸화는 후성유전학의 한 유형으로 유전자 발현을 조절하여 질병을 비롯한 다양한 생물학적 프로세스에 영향을 준다고 알려져 있다. 따라서 DNA 메틸화 정도와 인간 질병과의 연관성에 관한 연구는 질병의 원인 및 기전을 밝히고 메틸화 프로세스 조절을 통한 질병 치료 방법 개발을 위한 기반이 될 수 있다. 유전자 발현 조절 및 질병 발생은 많은 인자들의 복합적인 상호작용에 영향을 받으므로, 여러 위치에서의 메틸화 정도들의 고차원 조합을 이용한 질병과의 연관 관계 분석이 필수적이다. 본 연구에서는 진화 연산과 가중치 학습에 기반하여 유방암 발생과 연관되어 있는 메틸화 위치의 고차 상호작용을 탐색할 수 있는 방법을 제안한다.

Epigenetic Modification in Chronic Pain: A Literature Review (만성 통증과 후성유전학에 대한 문헌 고찰)

  • Song, Eun-Mo;Cho, Hong-Seok;Kim, Koh-Woon;Cho, Jae-Heung;Park, Hi-Joon;Song, Mi-Yeon
    • Journal of Korean Medicine Rehabilitation
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    • v.30 no.1
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    • pp.63-78
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    • 2020
  • Objectives To review the epigenetic modifications involved in chronic pain and to improve individualized intervention for the chronic pain. Methods Focused literature review. Results Significant laboratory and clinical data support that epigenetic modifications have a potential role for development of chronic pain. Conclusions Epigenetic approach may identify mechanisms critical to the development of chronic pain after injury, and may provide new pathways and target mechanisms for future treatment and individualized medicine.

Methylation Changes in Bipolar Disorder that can be detected through The Epigenetic Clock (후성유전학 시계를 통해 감지될 수 있는 양극성 장애의 메틸화 변화)

  • Yeon-Oh Jeong;Gwang-Won Cho
    • Journal of Integrative Natural Science
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    • v.16 no.3
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    • pp.75-80
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    • 2023
  • Bipolar disorder is a mental illness characterized by extreme mood and behavioral swings, such as highs of euphoria and lows of depression. It is a socially significant disorder in which people with the disorder experience intense mood swings and, for those with severe bipolar disorder, it is even difficult leading a normal life. High stress levels in people with mental illness can lead to neuroendocrine disruption, and it is strongly linked to aging. When the neuroendocrine system becomes vulnerable to these mental illnesses and stress, it is likely to accelerate aging. And it's the epigenetic clock that can measure the extent of this accelerated aging. The Epi clock, a pan tissue clock, measures aging through DNA methylation, and the degree of methylation is modified and changed by environmental conditions in the body. Therefore we wanted to check the changes in the epigenetic age of the patients with bipolar disorder. While we found no significant differences in epigenetic age, we did confirm the possibility that people with bipolar disorder have different methylation than normal people. We also found that the EPIC array data fit better on the Epi clock than on the Horvath clock with age-accelerated data from normal people.

Chromosome Redundancy and Tree Phenotype Variation in Autotetraploid Trifoliate Orange (동질 사배체 탱자에서 염색체 배가와 수체 표현형의 변이)

  • Oh, Eun Ui;Chae, Chi-Won;Kim, Sat-Byul;Lu, Jian Liang;Yun, Su-Hyun;Koh, Sang-Wook;Song, Kwan Jeong
    • Horticultural Science & Technology
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    • v.32 no.3
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    • pp.366-374
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    • 2014
  • The study was conducted to investigate the possibility that epigenetic DNA methylation causes tree phenotypic variation in autotetraploids through evaluating the phenotypic variation and DNA methylation in autotetraploids occurred spontaneously from diploid trifoliate orange. Chromosome analysis confirmed that fourteen trifoliate orange trees of selected by flow cytometry were tetraploids (2n = 4X = 36) without any aneuploids. Chromomycin A3 staining determined that these trees were all autotetraploid with doubled chromosome set. Tree phenotypes, such as tree height and width, branching number, length, and angle, internode length, and leaf characteristics, varied in the autotetraploids. Chlorophyll indices were diverse in the autotetraploids, but photosynthetic rates were not significantly different. In addition, a wide range of variation was observed in stomatal density and guard cell length. Analysis of global cytosine DNA methylation showed that there was a variation of the methylation level in autotetraploids. More than half of 14 autotetraploids had at least 2 times higher methylation level than diploid trifoliate orange. The results indicate that tree phenotypic variation in autotetraploids might be related to global DNA methylation for reducing gene redundancy.

Melanogenesis Promotion by 3-Deazaneplanocin A, a Specific Inhibitor of S-Adenosylhomocysteine Hydrolase, in B16/F10 Melanoma Cells (B16/F10 흑색종 세포에서 S-Adenosylhomocysteine Hydrolase 의 선택적 저해제 3-Deazaneplanocin A 에 의한)

  • Hwang, Yun Jeong;Boo, Yong Chool
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.2
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    • pp.107-121
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    • 2021
  • Skin hypopigmentation, which is observed in albinism or vitiligo, occurs when melanin synthesis is decreased by genetic, epigenetic, and other factors. To identify drug candidates that can promote melanin synthesis in cells, we screened an epigenetic modulator library consisting of 141 cell-permeable, small molecule drugs. B16/F10 murine melanoma cells were treated with each drug at 0.1 𝜇M and melanin synthesis and cell viability were subsequently monitored. As a result, (-)-neplanocin A, 3-deazaneplanocin A (DZNep), and DZNep hydrochloride were found to increase cellular melanin synthesis without causing cytotoxicity. Because these three structurally related drugs exhibited similar dose-dependent effects on melanin synthesis and cell viability, DZNep was selected as a representative drug for additional experiments. DZNep increased intracellular melanin content and tyrosinase (TYR) activity. DZNep also induced the expression of TYR, tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT) at the mRNA and protein levels. DZNep also induced the mRNA and protein expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanin synthesis. DZNep is a specific inhibitor of S-adenosylhomocysteine hydrolase and it caused the accumulation of S-adenosylhomocysteine that inhibits histone methyltransferases in cells. This study suggests that melanogenesis can be modulated by targeting S-adenosylhomocysteine hydrolase in certain cellular contexts.

Exocyclic GpC DNA methyltransferase from Celeribacter marinus IMCC12053 (Celeribacter marinus IMCC12053의 외향고리 GpC DNA 메틸트랜스퍼라아제)

  • Kim, Junghee;Oh, Hyun-Myung
    • Korean Journal of Microbiology
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    • v.55 no.2
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    • pp.103-111
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    • 2019
  • DNA methylation is involved in diverse processes in bacteria, including maintenance of genome integrity and regulation of gene expression. CcrM, the DNA methyltransferase conserved in Alphaproteobacterial species, carries out $N^6$-adenine or $N^4$-cytosine methyltransferase activities using S-adenosyl methionine as a co-substrate. Celeribacter marinus IMCC12053 from the Alphaproteobacterial group was isolated from a marine environment. Single molecule real-time sequencing method (SMRT) was used to detect the methylation patterns of C. marinus IMCC12053. Gibbs motif sampler program was used to observe the conversion of adenosine of 5'-GANTC-3' to $N^6$-methyladenosine and conversion of $N^4$-cytosine of 5'-GpC-3' to $N^4$-methylcytosine. Exocyclic DNA methyltransferase from the genome of strain IMCC12053 was chosen using phylogenetic analysis and $N^4$-cytosine methyltransferase was cloned. IPTG inducer was used to confirm the methylation activity of DNA methylase, and cloned into a pQE30 vector using dam-/dcm- E. coli as the expression host. The genomic DNA and the plasmid carrying methylase-encoding sequences were extracted and cleaved with restriction enzymes that were sensitive to methylation, to confirm the methylation activity. These methylases protected the restriction enzyme site once IPTG-induced methylases methylated the chromosome and plasmid, harboring the DNA methylase. In this study, cloned exocyclic DNA methylases were investigated for potential use as a novel type of GpC methylase for molecular biology and epigenetics.

Rediscovery of haploid breeding in the genomics era (유전체 시대에 반수체 육종의 재발견)

  • Lee, Seulki;Kim, Jung Sun;Kang, Sang-Ho;Sohn, Seong-Han;Won, So Youn
    • Journal of Plant Biotechnology
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    • v.43 no.1
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    • pp.12-20
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    • 2016
  • Advances in DNA sequencing technologies have contributed to revolutionary understanding of many fundamental biological processes. With unprecedented cost-effective and high-throughput sequencing, a single laboratory can afford to de novo sequence the whole genome for species of interest. In addition, population genetic studies have been remarkably accelerated by numerous molecular markers identified from unbiased genome-wide sequences of population samples. As sequencing technologies have evolved very rapidly, acquiring appropriate individual plants or populations is a major bottleneck in plant research considering the complex nature of plant genome, such as heterozygosity, repetitiveness, and polyploidy. This challenge could be overcome by the old but effective method known as haploid induction. Haploid plants containing half of their sporophytic chromosomes can be rapidly generated mainly by culturing gametophytic cells such as ovules or pollens. Subsequent chromosome doubling in haploid plants can generate stable doubled haploid (DH) with perfect homozygosity. Here, classical methodology to generate and identify haploid plants or DH are summarized. In addition, haploid induction by epigenetic regulation of centromeric histone is explained. Furthermore, the utilization of haploid plant in the genomics era is discussed in the aspect of genome sequencing project and population genetic studies.