• 생명과학회지
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• 제18권8호
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• pp.1132-1139
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• 2008

CpG island는 유전자의 발현 기작과 많은 관련이 있다. 포유동물 유전자의 약 $30{\sim}60$% 정도의 프로모터와 엑손부위에 CpG island가 존재 한다. 최근의 연구 결과에 따르면 CpG island의 과메틸화는 주요 암 억제유전자들을 불활성화 시켜 암을 일으키는 주요 요인이 되는 것으로 밝혀졌다. CpG island의 과메틸화는 거의 모든 암 종류에서 발견되고 있다. 따라서 CpG island를 검색하는 프로그램은 매우 중요한 의미를 갖는다. 그래서 D. Takai 와 P. A. Jones 등이 2002년 검증한 CpG island 정의 기준을 이용하여 윈도우 기반의 소프트웨어 프로그램인 CpGi를 개발하였다. CpGi는 Visual C++ 6.0로 구현하였으며, 입력서열 양식은 FASTA 포맷을 허용하도록 구성하였다. CpGi의 검색 성능을 평가하기 위해 2개의 인간 Contig, 즉, AP00524 (22번 염색체)와 NT_029490.3 (21번 염색체) 등을 대상으로 기존의 다른 CpG island 검색 프로그램인 Emboss-CpGPlot 및 CpG Island Searcher 등과 검색결과를 비교 분석하였다. CpGi에 의한 검색 결과는 다른 두 프로그램에 비해 같거나 오히려 보다 정확한 검색 결과를 보여주었다. CpGi는 사용자 친화적인 윈도우 인터페이스로 구현되어 있어 사용자가 프로그램을 구동하고 이용하기 매우 쉽고, 분석결과에 대한 이해도 용이하다. 본 프로그램은 사용자가 지정한 파라미터 값들(%GC, Obs (CpG)/Exp (CpG), 분석 윈도우 크기, 스텝크기, Gap 허용치, #CG)에 의해 CpG island의 위치를 결정하고, G+C%와 CpG island의 위치를 시각적으로 보여준다. 결과적으로, CpGi는 CpG island 관련 실험 연구자들뿐만 아니라 대용량 서열 분석 및 주석 작업을 위해 매우 유용한 도구로 활용될 수 있을 것이다.

• 전기학회논문지
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• 제65권7호
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• pp.1236-1241
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• 2016

Cancer has been the most frequent in Korea, and pathogenesis and progression of cancer have been known to be occurred through various causes and stages. Recently, the research of chromosomal and genetic disorder and the research about prognostic factor to predict occurrence, recurrence and progress of chromosomal and genetic disorder have been performed actively. In this paper, we analyzed DNA methylation data downloaded from TCGA (The Cancer Genome Atlas), open database, to research bladder cancer which is the most frequent among urinary system cancers. Using three level of methylation data which had the most preprocessing, 59 candidate CpG island were extracted from 480,000 CpG island, and then we analyzed extracted CpG island applying data mining technique. As a result, cg12840719 CpG island were analyzed significant, and in Cox's regression we can find the CpG island with high relative risk in comparison with other CpG island. Shown in the result of classification analysis, the CpG island which have high correlation with bladder cancer are cg03146993, cg07323648, cg12840719, cg14676825 and classification accuracy is about 76%. Also we found out that positive predictive value, the probability which predicts cancer in case of cancer was 72.4%. Through the verification of candidate CpG island from the result, we can utilize this method for diagnosing and treating cancer.

• Genomics & Informatics
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• 제8권1호
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• pp.58-61
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• 2010

CpG is the pair of nucleotides C and G, appearing successively, in this order, along one DNA strand. It is known that due to biochemical considerations CpG is relatively rare in most DNA sequences. However, in particular subsequences, which are a few hundred to a few thousand nucleotides long, the couple CpG is more frequent. These subsequences, called CpG islands, are known to appear in biologically more significant parts of the genome. The ability to identify CpG islands along a chromosome will therefore help us spot its more significant regions of interest, such as the promoters or 'start' regions of many genes. In this respect, I developed the CpG islands search tool, CpG Islands Detector, which was implemented in JAVA to be run on any platform. The window-based graphical user interface of CpG Islands Detector may facilitate the end user to employ this tool to pinpoint CpG islands in a genomic DNA sequence. In addition, this tool can be used to highlight potential genes in genomic sequences since CpG islands are very often found in the 5' regions of vertebrate genes.

• Journal of Genetic Medicine
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• 제6권1호
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• pp.1-7
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• 2009

프로모터 CpG island 과메틸화와 히스톤 변경으로 대변되는 후성유전적 변화는 거의 모든 종류의 암에서 발견되는 중요한 발암기전이다. 인간유전자의 60-70% 가량이 프로모터에 CpG islands를 가지고 있으며, 이 유전자들 중 일부가 과메틸화됨으로써 해당유전자의 발현이 차단되고, 종양억제기능이 소실되어 종양세포의 성장을 촉진하게 된다. 암에는 프로모터 CpG island 과메틸화라는 국소적 변화 이외에, 유전체 전반에 걸친 탈메틸화를 동시에 보이는 경우가 대부분인데, 이러한 유전체 저메틸화는 염색체 불안정성과 밀접한 연관관계가 있다. 국소적 과메틸화와 전반적인 저메틸화라는 이러한 상반된 DNA 메틸화 변화는 암세포뿐만 아니라 그 전단계 병변인 이 형성 병변에서도 관찰된다. 프로모터CpG island 과메틸화는 유전자 발현억제 기전으로서의 중요성뿐만 아니라 종양표지자로서의 중요성이 부각되고 있다. 즉, 정상세포에서는 관찰되지 않으면서 암세포에서만 관찰되는 프로모터 CpG island 과메틸화는 암세포의 바이오마커로서의 가치가 있으며, 이를 이용하여 체액에서 암을 진단하려는 시도들이 이루어지고, 이를 활용한 암의 분자진단방법이 개발되고 있다. 또한 이러한 DNA 메틸화는 암환자의 예후 판정이나 항암치료제의 감수성 결정 등에 활용되고 있다. 본 원고에서는 인체 암세포에서의 DNA 메틸화 변화에 관하여 소개하고자 한다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1141-1149
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• 2018

Objective: Cluster of differentiation 4 protein (CD4) gene is an important immune related gene which plays a significant role in T cell development and host resistance during viral infection. Methods: In order to unravel the relationship of CpG island methylation level of CD4 gene with its gene expression and T lymphocyte subpopulation traits, we used one typical Chinese indigenous breed (Dapulian, DP) and one commercial breed (Landrace), then predicted the CpG island of CD4 gene, determined the methylation status of CpG sites by bisulfite sequencing polymerase chain reaction (BSP), and carried out the correlation analyses of methylation frequencies of CpG sites with mRNA expression and T lymphocyte subpopulation traits. Results: There was one CpG island predicted in the upstream -2 kb region and exon one of porcine CD4 gene, which located 333 bp upstream from the start site of gene and contained nine CpG sites. The correlation analysis results indicated that the methylation frequency of CpG_2 significantly correlated with CD4 mRNA expression in the DP and Landrace combined population, though it did not reach significance level in DP and Landrace separately. Additionally, 15 potential binding transcription factors (TFs) were predicted within the CpG island, and one of them (Jumonji) contained CpG_2 site, suggesting that it may influence the CD4 gene expression through the potential binding TFs. We also found methylation frequency of CpG_2 negatively correlated with T lymphocyte subpopulation traits CD4+CD8-CD3-, CD4-CD8+CD3- and CD4+/CD8+, and positively correlated with CD4-CD8+CD3+ and CD4+CD8+CD3+ (for all correlation, p<0.01) in DP and Landrace combined population. Thus, the CpG_2 was a critical methylation site for porcine CD4 gene expression and T lymphocyte subpopulation traits. Conclusion: We speculated that increased methylation frequency of CpG_2 may lead to the decreased expression of CD4, which may have some kind of influence on T lymphocyte subpopulation traits and the immunity of DP population.

• Parasites, Hosts and Diseases
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• 제55권2호
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• pp.115-120
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• 2017

Encystation mediating cyst specific cysteine proteinase (CSCP) of Acanthamoeba castellanii is expressed remarkably during encystation. However, the molecular mechanism involved in the regulation of CSCP gene expression remains unclear. In this study, we focused on epigenetic regulation of gene expression during encystation of Acanthamoeba. To evaluate methylation as a potential mechanism involved in the regulation of CSCP expression, we first investigated the correlation between promoter methylation status of CSCP gene and its expression. A 2,878 bp of promoter sequence of CSCP gene was amplified by PCR. Three CpG islands (island 1-3) were detected in this sequence using bioinformatics tools. Methylation of CpG island in trophozoites and cysts was measured by bisulfite sequence PCR. CSCP promoter methylation of CpG island 1 (1,633 bp) was found in 8.2% of trophozoites and 7.3% of cysts. Methylation of CpG island 2 (625 bp) was observed in 4.2% of trophozoites and 5.8% of cysts. Methylation of CpG island 3 (367 bp) in trophozoites and cysts was both 3.6%. These results suggest that DNA methylation system is present in CSCP gene expression of Acanthamoeba. In addition, the expression of encystation mediating CSCP is correlated with promoter CpG island 1 hypomethylation.

• 생명과학회지
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• 제15권5호
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• pp.802-808
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• 2005

사람의 Disabled-2 (Dab2)는 정상세포에서 c-Fos의 발현을 억제하여 세포 성장을 조절하는 암억제 유전자로 추정되어 지고 있다. 많은 암세포에서 Dab2는 유방과 난소의 정상세포에서는 발현이 되지만, 약 $85\%$의 유방과 난소의 종양세포에서는 발현이 줄어들거나, 발현이 억제되는 것으로 알려져 있다. 본 연구에서는 bisulfite 반응에 의한 염기서열 분석법과 MSP방법 등을 이용하여 유방암 세포주인 MDA MB-231세포에서 Dab2 유전자의 promoter상에 존재하는 Cpg island의 methylation된 상태를 분석하였다. 그 결과, 사람의 정상 자궁내막세포에서는 Dab2 promoter 부위가 완전하게 methylation되어 있지 않았다. 그러나 MDA MB-231세포에서는 TATA box 근처 의 CpG dinucleotide에서 비정상적으로 methylation되어 있었다. 이런 비정상적인 CpG dinucleotide의 methylation은 MDA MB-231세포를 5-azacytidine으로 처리하였을 때 methylation이 풀리고, Dab2의 발현이 회복되는 것으로 나타났다. 따라서 인간 유방암 세포주인 MBA MB-231세포에서 Dab2의 발현억제는 Dab2 유전자의 promoter부위의 CpG island의 비정상적인 methylation과 관련이 있는 것으로 여겨진다.

• ALGAE
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• 제29권3호
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• pp.227-235
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• 2014

The red seaweed, Gracilaria tikvahiae McLachlan, was cultivated in open water farms in urbanized estuaries of Long Island Sound (26-30 psu of salinity) and New York City (20-25 psu), USA in 2011. Plants were harvested monthly from summer (August, $24^{\circ}C$) to fall (November, $13^{\circ}C$) and analyzed for total nitrogen, protein, and amino acid content. On a dry matter (DM) basis, nitrogen and protein significantly increased over the harvest period until October and then plateaued. Nitrogen increased from $22{\pm}1g\;kg^{-1}$ DM in August to $39{\pm}3g\;kg^{-1}$ DM in October (p < 0.001). Protein increased from $107{\pm}13g\;kg^{-1}$ DM in August to $196{\pm}5g\;kg^{-1}$ DM in November (p < 0.001). With two exceptions, amino acid concentrations expressed on a crude protein (CP) basis were similar over the harvest period. Essential amino acids accounted for $48{\pm}1%$ of all amino acids present with lysine and methionine averaging $56{\pm}2g\;kg^{-1}$ CP and $18{\pm}1g\;kg^{-1}$ CP, respectively. Histidine was underrepresented among essential amino acids and averaged $13{\pm}1g\;kg^{-1}$ CP. Taurine ranged from 2.1 to $3.2g\;kg^{-1}$ DM. With its moderate levels of lysine, methionine and taurine, ocean farmed G. tikvahiae has the potential of overcoming many nutrient deficiencies currently associated with terrestrial plant ingredients in alternative feeds for fish and shrimp.

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2006년도 제47회 학술심포지움 및 추계국제학술대회
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• pp.35.2-35.2
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• 2006

• Genomics & Informatics
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• 제9권4호
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• pp.194-196
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• 2011

Promoter prediction is a very important problem and is closely related to the main problems of bioinformatics such as the construction of gene regulatory networks and gene function annotation. In this context, we developed an integrated promoter prediction program using hybrid methods, PromoterWizard, which can be employed to detect the core promoter region and the transcription start site (TSS) in vertebrate genomic DNA sequences, an issue of obvious importance for genome annotation efforts. PromoterWizard consists of three main modules and two auxiliary modules. The three main modules include CDRM (Composite Dependency Reflecting Model) module, SVM (Support Vector Machine) module, and ICM (Interpolated Context Model) module. The two auxiliary modules are CpG Island Detector and GCPlot that may contribute to improving the predictive accuracy of the three main modules and facilitating human curator to decide on the final annotation.