• 식물조직배양학회지
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• 제27권5호
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• pp.359-366
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• 2000

Epigenetics represents a chromatin-mediated transcriptional repression which plays a control role in both animal and plant development. A number of different mechanisms have been described to be involved in the formation of chromatin structure: especially DNA methylation, nucleosomal histone modification, DNA replication timing, and binding of chromatin remodelling proteins. Epigenetic phenomena include genomic imprinting, dosage compensation of X-chromosome linked genes, mutual allelic interactions, paramutation, transvection, silencing of invasive DNA sequences, etc. They are often unstable and inherited in a non-Mendelian way. A number of epigenetic defects has been preferentially described in floral development. Here, epigenetic phenomena in model angiosperm plants and their corresponding mechanisms are reviewed.

• Journal of Microbiology and Biotechnology
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• 제27권8호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4539-4543
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• 2014

Since the epigenetic alteration in tumor cells can be reversed by the dietary polyphenol quercetin (Q) or butyrate (B) with chemopreventive activity, suggesting that Q or B can be used for chemopreventive as well as therapeutic agent against tumors. In this study the polyphenol flavonoid quercetin (Q) or sodium butyrate (B) suppressed human esophageal 9706 cancer cell growth in dose dependent manner, and Q combined with B (Q+B) could further inhibit Eca9706 cell proliferation than that induced by Q or B alone, compared with untreated control group (C) in MTT assay. The reverse expressions of global DNMT1, $NF-{\kappa}Bp65$, HDAC1 and Cyclin D1 were down-regulated, while expressions of caspase-3 and $p16INK4{\alpha}$ were up-regulated, compared with the C group in immunoblotting; the down-regulated HDAC1-IR (-immunoreactivity) with nuclear translocation, and up-regulated E-cadherin-IR demonstrated in immunocytochemistry treated by Q or B, and Q+B also displayed further negatively and positively modulated effects compared with C group. The order of methylation specific (MS) PCR of $p16INK4{\alpha}$: C>B/Q>Q+B group, while the order of E-cadherin expression level was contrary, Q+B>Q/B>C group. Thus, Q/B, especially Q+B display reverse effect targeting both altered DNA methylation and histone acetylation, acting as histone deacetylase inhibitor mediated via epigenetic-$NF-{\kappa}B$ cascade signaling.

• 생물정신의학
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• 제15권4호
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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.

• Animal cells and systems
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• 제16권1호
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• pp.1-10
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• 2012

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2001년도 춘계학술발표대회
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• pp.49-49
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• 2001

To elucidate overall changes in DNA methylation that occurs by inappropriate epigenetic control during ageing, we compared fetal bovine fibroblasts and their aged neomycin-resistant versions using bisulfite-PCR technology. Reduction in DNA methylation was observed in euchromatic repeats (18S-rRNA/art2) and promoter regions of sing1e-copy genes (the cytokeratin/-lactoglobulin/interleukin-13 genes). Contrastingly, a stable maintenance of DNA methylation was revealed in various heterochromatic sequences (satellite I/IIalphoid and Bov-B). The differential inheritance modes of DNA methylation was confirmed through the analysis of individual neomycin-resistant clones. These global, multi-loci analyses provide evidence on the tendency of differential epigenetic modification between genomic DNA regions during ageing.

• Molecules and Cells
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• 제38권6호
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• pp.518-527
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• 2015

Controlled release of medications remains the most convenient way to deliver drugs. In this study, we precipitated gold nanoparticles with quercetin. We loaded gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles (NQ) and tested the biological activity of NQ on HepG2 hepatocarcinoma cells to acquire the sustained release property. We determined by circular dichroism spectroscopy that NQ effectively caused conformational changes in DNA and modulated different proteins related to epigenetic modifications and c ell cycle control. The mitochondrial membrane potential (MMP), reactive oxygen species (ROS), cell cycle, apoptosis, DNA damage, and caspase 3 activity were analyzed by flow cytometry, and the expression profiles of different anti- and pro-apoptotic as well as epigenetic signals were studied by immunoblotting. A cytotoxicity assay indicated that NQ preferentially killed cancer cells, compared to normal cells. NQ interacted with HepG2 cell DNA and reduced histone deacetylases to control cell proliferation and arrest the cell cycle at the sub-G stage. Activities of cell cycle-related proteins, such as $p21^{WAF}$, cdk1, and pAkt, were modulated. NQ induced apoptosis in HepG2 cells by activating p53-ROS crosstalk and induces epigenetic modifications leading to inhibited proliferation and cell cycle arrest.

• 생명과학회지
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• 제33권9호
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• pp.730-735
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• 2023

지난 10년 동안 인공지능의 도움으로 노화를 정량화하기 위한 수많은 연구가 수행되었다. DNA 메틸화 데이터를 사용하여 다양한 모델이 개발되었으며 흔히 후성유전학적 시계라고 불린다. 후성유전학적 나이 가속화는 일반적으로 질병 상태와도 주로 연관이 있어 보인다. 조현병은 가속 노화 가설과 관련있는 정신질병으로 심각한 정신적, 신체적 스트레스를 동반한다. 다른 심리 질환과 비교했을 때 이 질병은 젊은 사람들에서 높은 사망률과 질병률을 유발한다. 과거 연구에서는 이 질병이 가속 노화 가설과 연관있다고 알려져 있었다. 이번 연구에서는 조현병 환자의 후성유전학적 나이 가속도 변화를 통해 질병에 대한 후성유전학적 통찰을 얻고자 하였다. 후성유전학적 나이 가속화를 측정하기 위해 두 가지 다른 DNA 메틸화 시계 모델을 사용했으며 이는 범조직 모델인 Horvath clock과 Epi clock을 사용하였다. 우리는 Horvath clock과 Epi clock이 모두 호환되는 450k 어레이 데이터를 사용하였다. 그 결과, Epi clock을 사용했을 때 환자샘플에서 후성유전학적 나이 가속화가 더 느리다는 것을 발견했다. Epi clock이 질병으로 인한 DNA 메틸화 변화를 잘 감지해낼 수 있음을 알아내었다. 또한 Epi clock에서 대조군과 환자군에서 차등적으로 메틸화된 CpG 부위를 분석하고 경로 농축 분석을 수행한 결과, 대부분의 CpG가 신경 세포 과정에 관여한다는 사실을 발견했다.

• 생명과학회지
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• 제34권7호
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• pp.520-530
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• 2024

종양 억제 유전자(TSG)는 세포 항상성을 유지하는 데 중요한 역할을 한다. 이러한 유전자의 기능이 상실되면 세포 가소성(cellular plasticity)이 유발되어 다양한 암, 특히 공격적인 성향을 가진 소세포 폐암(SCLC)이 발생할 수 있다. SCLC는 주로 후성학적 조절인자를 암호화하는 유전자에서 발생하는 다수의 기능 상실 돌연변이에 의해 유발된다. 이러한 돌연변이는 직접적으로 표적화하기 어렵기 때문에 치료제 개발이 어려운 상황이다. 그러나 이러한 돌연변이로 인한 분자적 변화를 이해하면 종양 치료 전략을 개발하는데 큰 도움이 될 수 있다. 우리는 SCLC의 이질적인 유전체 환경에도 불구하고 환자의 종양에서 발생하는 돌연변이의 영향이 악성 종양을 유발하는 몇 가지 중요한 경로로 수렴되고 있음을 확인하였다. 특히, 후성학적 변화는 전사 조절 장애를 초래하여 돌연변이 세포가 면역 회피 및 높은 전이 능력을 가진 매우 가소성이 높은 상태로 진입하게 한다. 본 논문에서는 반대 기능을 가진 후성학적 조절인자의 불균형이 면역 인식 마커의 상실로 이어져 종양 세포가 면역 체계로부터 효과적으로 회피하는 과정을 보여주는 연구들을 강조하였다. 또한 후성학적 조절인자가 신경내분비 세포 특성을 유지하는 역할과 비정상적인 전사 조절이 종양의 발달 및 진행 중 상피간엽이행(EMT)를 촉진하는 방법에 대해 서술하였다. 이 경로들은 별개의 것처럼 보이지만, 흔히 공통된 분자와 매개체를 공유하고 있음을 확인하였다. 빈번하게 변화하는 후성학적 조절인자 간의 연결을 이해하면 SCLC 및 유사한 돌연변이를 가진 다른 암의 발달과 진행의 분자적 메커니즘에 대한 귀중한 통찰력을 제공하여 예방 및 치료법 개발에 기여할 수 있을 것이다.

• Genomics & Informatics
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• 제8권4호
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• pp.185-193
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• 2010

Histone deacetylation and demethylation are epigenetic mechanisms implicated in cancer. Studies regarding the role of modulation of gene expression utilizing the histone deacetylase inhibitor scriptaid and the demethylating agent 5-azacytidine in HL-60 leukemia cells have been limited. We studied the possibility of recovering epigenetically silenced genes by scriptaid and 5-azacytidine in human leukemia cells by DNA microarray analysis. The first group was leukemia cells that were cultured with 5-azacytidine. The second group was cultured with scriptaid. The other group was cultured with both agents. Two hundred seventy newly developed genes were expressed after the combination of 5-azacytidine and scriptaid. Twenty-nine genes were unchanged after the combination treatment of 5-azacytidine and scriptaid. Among the 270 genes, 13 genes were differed significantly from the control. HPGD, CPA3, CEACAM6, LOC653907, ETS1, RAB37, PMP22, FST, FOXC1, and CCL2 were up-regulated, and IGLL3, IGLL1, and ASS1 were down-regulated. Eleven genes associated with oncogenesis were found among the differentially expressed genes: ETS1, ASCL2, BTG2, BTG1, SLAMF6, CDKN2D, RRAS, RET, GIPC1, MAGEB, and RGL4. We report the results of our leukemia cell microarray profiles after epigenetic combination therapy with the hope that they are the starting point of selectively targeted epigenetic therapy.