• 한국균학회지
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• 제31권2호
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• pp.103-113
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• 2003

국내의 가지과 작물에서 분리한 Alternaria 25 균주를 공시하여 분생포자의 형태적 특징을 조사하였고 A. solani와 A. tomaotphilad의 대표균주와 비교하였다. 분리균주 중 형태적으로 구별되는 몇 균주들과 대표균주를 공시하여 감자, 토마토, 가지, 고추에 대한 병원성 검정을 실시하였다. 대표균주를 포함한 Alternaria 17개 균주를 공시하여 ITS 영역과 histone h3 유전자의 염기서열분석, URP (universal rice primer)에 의한 핵산지문분석을 실시하였다. Alternaria 균주들은 분생포자의 형태적 특징에 의하여 A. tomaotophila(ATO), A. solani(ASO) 및 미동정의 Alternaria sp.(ASP)의 group으로 나눌 수 있었고 A. solani(ASO)는 분생포자 부리(beak)의 특징에 의하여 다시 ASO(1)과 ASO(2)의 2 type으로 나눌 수 있었다. ATO와 ASO 균주들은 실험에 사용한 감자, 토마토, 가지, 고추에 모두 병원성이 있었고 ATO 균주는 특히 토마토에 강한 병원성이 있었으나, ASP 균주는 감자에만 병원성이 있었다. 이 연구에서 사용한 molecular marker중 ITS와 histon H3 유전자의 염기서열 분석은 4개의 형태적 group을 명확히 구분할 수 없었지만, URP-PCR 핵산지문분석법은 이들 group을 명확히 구분할 수 있었다. 분생포자의 형태, 병원성검정, 분자생물학적 특징을 종합할 때 토마토 겹무늬병에 관여하는 A. tomatophila는 감자겹둥근무늬병에 관여하는 A. solani와 뚜렷이 구분할 수 있었다. 또한 감자에서 분리한 Alternaria sp.(ASP)는 A. solani(ASO)와 형태적으로 유사하였지만 분생포자의 폭이 두껍고 부리(beak)가 작다는 점에서 ASO와 구별되었으며 가지과 작물에서 보고된 바 없는 신종으로 추정되었다.

• Molecules and Cells
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• 제37권1호
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• pp.43-50
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• 2014

Jumonji domain-containing proteins (JMJD) catalyze the oxidative demethylation of a methylated lysine residue of histones by using $O_2$, ${\alpha}$-ketoglutarate, vitamin C, and Fe(II). Several JMJDs are induced by hypoxic stress to compensate their presumed reduction in catalytic activity under hypoxia. In this study, we showed that an H3K27me3 specific histone demethylase, JMJD3 was induced by hypoxia-inducible factor (HIF)-$1{\alpha}/{\beta}$ under hypoxia and that treatment with Clioquinol, a HIF-$1{\alpha}$ activator, increased JMJD3 expression even under normoxia. Chromatin immunoprecipitation (ChIP) analyses showed that both HIF-$1{\alpha}$ and its dimerization partner HIF-$1{\beta}$/Arnt occupied the first intron region of the mouse JMJD3 gene, whereas the HIF-$1{\alpha}/{\beta}$ heterodimer bound to the upstream region of the human JMJD3, indicating that human and mouse JMJD3 have hypoxia-responsive regulatory regions in different locations. This study shows that both mouse and human JMJD3 are induced by HIF-1.

• 한국자원식물학회지
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• 제20권6호
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• pp.518-523
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• 2007

Lunasin is small subunit peptide of coded from Gm2S-1 gene in soybean. It has been previously demonstrated that lunasin is a novel and promising cancer preventive peptide. Lunasin peptide is found only in the seed and not other tissues. And lunasin peptide starts to appear at 5 weeks after flowering and remains in the mature seed. We report here firstly lunasin peptide identified from soybean callus induced by the tissue culture and demonstrate its anticancer properties. The lunasin was identified and purified from soybean callus aged for 6 months. The callus lunasin($1{\mu}M$) inhibited the acetylation of histone H3 and H4 by 58.8% and 56.5%, respectively. And it fully inhibited foci formation compared to the values of the positive control(no lunasin) and negative control(no MCA). Purified lunasin was able to internalize into the cell and localized in the nucleus.

• Molecules and Cells
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• 제26권1호
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• pp.93-99
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• 2008

Transcriptional silencing is regulated by promoter methylation and histone modifications such as methylation and acetylation. We constructed a Schizosaccaromyces pombe reporter strain, KCT120a, to identify modifiers of transcriptional silencing, by inserting the $ura4^+$ gene into a heterochromatic telomere region. Two compounds inhibited the activity of histone deacetylases, induced acetylation of histone H3 and caused apoptotic cell death in HeLa cells. Expression of gelsolin and $p21^{waf1/cip1}$ also increased, as it does in response to HDAC inhibitors such as TSA. Therefore, these compounds appear to be potent inhibitors of HDACs, and hence potential anti-cancer drugs. Our observations suggest that a yeast cell-based assay system for transcriptional silencing may be useful for identifying histone deacetylase inhibitors and other agents affecting chromatin remodeling.

• BMB Reports
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• 제54권8호
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• pp.413-418
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• 2021

ErbB3-binding protein 1 (EBP1) is a multifunctional protein associated with neural development. Loss of Ebp1 leads to upregulation of the gene silencing unit suppressor of variegation 3-9 homolog 1 (Suv39H1)/DNA (cytosine 5)-methyltransferase (DNMT1). EBP1 directly binds to the promoter region of DNMT1, repressing DNA methylation, and hence, promoting neural development. In the current study, we showed that EBP1 suppresses histone methyltransferase activity of Suv39H1 by promoting ubiquitin-proteasome system (UPS)-dependent degradation of Suv39H1. In addition, we showed that EBP1 directly interacts with Suv39H1, and this interaction is required for recruiting the E3 ligase MDM2 for Suv39H1 degradation. Thus, our findings suggest that EBP1 regulates UPS-dependent degradation of Suv39H1 to govern proper heterochromatin assembly during neural development.

• 대한유전성대사질환학회지
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• 제20권1호
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• pp.1-13
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• 2020

Gaucher disease (GD)는 glucocerebrosidase 유전자(GBA)의 돌연변이에 의하여 발병하는 전세계적으로 가장 유병율이 높은 리소좀 축적질환이다. GD는 신경학적인 증상의 유무에 따라 3가지 임상형으로 구분된다. 신경병증 GD인 2형과 3형의 경우는 대뇌에서 glucosylceramide (GlcCer)와 glucosylsphingosine (GlcSph)의 농도가 증가하면서 신경세포의 심각한 손실이 야기되는 특징을 보인다. 신경교종에서 유래한 H4 세포를 GD에서 증가하는 기질인 GluCer와 GlcSph를 첨가하여 배양하였을 때, 심각한 DNA손상과 더불어 세포의 사멸이 야기되는 것과 이러한 신경세포의 사멸은 GluCer 보다는 GlcSph을 처리하였을 때 더 현저하게 증가하는 것을 관찰하였다. H4 세포에 히스톤 탈아세틸화 효소(HDAC) 6의 저해제인 tubacin과 GlcSph을 함께 처리하였을 경우에는 DNA손상은 물론 GlcSph에 의하여 유도된 세포사멸과 관련된 단백질 인자들의 발현이 모두 감소되었다. 본 연구를 통해 GlcSph이 세포사멸을 통하여 신경병증 GD의 발병에 주요한 역할을 한다는 것을 알 수 있었고, HDAC6 저해제가 신경병증 GD 환자를 위한 치료제 후보물질로 제시될 수 있는 가능성을 확인하였다.

• Molecules and Cells
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• 제42권1호
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• pp.17-27
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• 2019

Ubiquitin-specific protease 44 (USP44) has been implicated in tumor progression and metastasis across various tumors. However, the function of USP44 in prostate cancers and regulatory mechanism of histone-modifying enzymes by USP44 in tumors is not well-understood. Here, we found that enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, is regulated by USP44. We showed that EZH2 is a novel target of USP44 and that the protein stability of EZH2 is upregulated by USP44-mediated deubiquitination. In USP44 knockdown prostate cancer cells, the EZH2 protein level and its gene silencing activity were decreased. Furthermore, USP44 knockdown inhibited the tumorigenic characteristics and cancer stem cell-like behaviors of prostate cancer cells. Inhibition of tumorigenesis caused by USP44 knockdown was recovered by ectopic introduction of EZH2. Additionally, USP44 regulates the protein stability of oncogenic EZH2 mutants. Taken together, our results suggest that USP44 promotes the tumorigenesis of prostate cancer cells partly by stabilizing EZH2 and that USP44 is a viable therapeutic target for treating EZH2-dependent cancers.

• Asian Pacific Journal of Cancer Prevention
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• 제13권7호
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• pp.3173-3178
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• 2012

The enhancer of zeste homolog 2 (EZH2) methyl transferase and histone 3 lysine 27 (H3K27me3) protein can repress gene transcription, and their aberrant expression has been observed in various human cancers. This study determined their expression levels in gastric cancer tissues with reference to clinicopathological features and patient survival. We collected 117 gastric cancer and corresponding normal tissues for immunohistochemistry analysis. In gastric cancers, 82/117 (70.1%) were positive for EZH2 and 66/117 (56.4%) for H3K27me3 proteins in contrast to only 5.41% and 7.25% of normal gastric mucosa specimens, respectively. Kaplan-Meier survival data showed the average overall and disease-free survival of EZH2 high expression patients was 25.2 and 20.2 months, respectively, shorter than that with EZH2 low expression (40.5 and 35.9 months). The average overall survival and disease-free survival of high H3K27me3 expression patients was 23.4 and 17.4 months, shorter than without H3K27me3 expression (37.6 and 34.5 months). The average overall survival and disease-free survival of patients with both EZH2 and H3K27me3 expression was 18.8 and 12.9 months, respectively, shorter than that with either alone (34.7 and 31.2 months) or with low levels of both (43.9 and 39.9 months). Multivariate Cox regression analysis showed that H3K27me3 and EZH2 expression, tumor size differentiation and clinical stage were all independent prognostic factors for predicting patient survival. This study demonstrated that detection of both EZH2 and H3K27me3 proteins can predict poor survival of gastric cancer patients, superior to single protein detection. In addition, H3K27me3 and EZH2 protein expression could predict lymph node metastasis.

• BMB Reports
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• 제48권7호
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• pp.401-406
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• 2015

Here we report that the H3K9 demethylase KDM3B represses transcription of the angiogenesis regulatory gene, ANGPT1. Negative regulation of ANGPT1 by KDM3B is independent of its Jumonji (JmjC) domain-mediated H3K9 demethylase activity. We demonstrate that KDM3B downregulates ANGPT1 via interaction with SMRT, and suggest that the repressor complex is formed at the promoter area of ANGPT1. Using MTT and wound healing assays, depletion of KDM3B was found to increase cell proliferation and cell motility, indicating that KDM3B has a role in angiogenesis. [BMB Reports 2015; 48(7): 401-406]

• 생명과학회지
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• 제29권9호
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• pp.1002-1009
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• 2019

생애 초기 유해 경험은 우울증의 위험성을 높이며, 성인기 스트레스의 민감성에 영향을 미칠 수 있다. 출생 후 모성 분리(MS)로 인한 성인기 스트레스(장기간 예측 불가능한 스트레스; CUS)의 취약성에 p11 유전자의 후성유전기전이 영향을 미치는 지를 확인하였다. 출생 직후부터 21일 동안 하루 3시간 동안 새끼 생쥐를 어미 생쥐로부터 분리시켜 새끼 생쥐가 성체가 되었을 때 CUS를 3주 동안 매일 적용하였다. Real time PCR기법으로 해마의 p11 발현 양을 측정하였고, 염색질 면역 침전 분석법으로 p11 promoter의 히스톤 H3 아세틸화 및 메틸화 양을 측정하였다. 강제수영검사에서 우울 유사 행동을 측정하였다. MS군 및 CUS군은 p11 mRNA 발현 양을 유의하게 감소시켰으며, MS+CUS군은 CUS군에 비해 p11 발현 양을 유의하게 증가시켰다. 또한 MS+CUS군은 CUS군에 비해 H3 아세틸화를 감소시켰다. 이러한 감소는 HDAC5 mRNA 발현 증가와 일치하였다. MS+CUS군은 CUS군에 비해 H3K4 메틸화를 감소시켰으며, H3K27 메틸화를 증가시켰다. 강제수영검사에서 p11 발현이 가장 많이 감소된 MS+CUS군이 대조군에 비해 더 긴 부동 시간을 나타내었다. 출생 후 모성 분리를 경험하고 성체 기간에 스트레스를 함께 받은 생쥐는 성체기간에만 스트레스를 받은 생쥐보다 훨씬 더 큰 후성유전 변화를 보여주었다. 생애 초기 유해 경험은 해마에서 p11 유전자의 히스톤 변형을 통해 성체 스트레스 효과를 더 악화시키는 것으로 생각된다.