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Decoding the genome with an integrative analysis tool: Combinatorial CRM Decoder
Kang, Keunsoo,Kim, Joomyeong,Chung, Jae Hoon,Lee, Daeyoup Oxford University Press 2011 Nucleic acids research Vol.39 No.17
<P>The identification of genome-wide <I>cis</I>-regulatory modules (CRMs) and characterization of their associated epigenetic features are fundamental steps toward the understanding of gene regulatory networks. Although integrative analysis of available genome-wide information can provide new biological insights, the lack of novel methodologies has become a major bottleneck. Here, we present a comprehensive analysis tool called combinatorial CRM decoder (CCD), which utilizes the publicly available information to identify and characterize genome-wide CRMs in a species of interest. CCD first defines a set of the epigenetic features which is significantly associated with a set of known CRMs as a code called ‘trace code’, and subsequently uses the trace code to pinpoint putative CRMs throughout the genome. Using 61 genome-wide data sets obtained from 17 independent mouse studies, CCD successfully catalogued ∼12 600 CRMs (five distinct classes) including polycomb repressive complex 2 target sites as well as imprinting control regions. Interestingly, we discovered that ∼4% of the identified CRMs belong to at least two different classes named ‘multi-functional CRM’, suggesting their functional importance for regulating spatiotemporal gene expression. From these examples, we show that CCD can be applied to any potential genome-wide datasets and therefore will shed light on unveiling genome-wide CRMs in various species.</P>
A Genome-Wide Methylation Approach Identifies a New Hypermethylated Gene Panel in Ulcerative Colitis
Kang, Keunsoo,Bae, Jin-Han,Han, Kyudong,Kim, Eun Soo,Kim, Tae-Oh,Yi, Joo Mi MDPI AG 2016 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.17 No.8
<P>The cause of inflammatory bowel disease (IBD) is still unknown, but there is growing evidence that environmental factors such as epigenetic changes can contribute to the disease etiology. The aim of this study was to identify newly hypermethylated genes in ulcerative colitis (UC) using a genome-wide DNA methylation approach. Using an Infinium HumanMethylation450 BeadChip array, we screened the DNA methylation changes in three normal colon controls and eight UC patients. Using these methylation profiles, 48 probes associated with CpG promoter methylation showed differential hypermethylation between UC patients and normal controls. Technical validations for methylation analyses in a larger series of UC patients (<I>n</I> = 79) were performed by methylation-specific PCR (MSP) and bisulfite sequencing analysis. We finally found that three genes (<I>FAM217B</I>, <I>KIAA1614</I> and <I>RIBC2</I>) that were significantly elevating the promoter methylation levels in UC compared to normal controls. Interestingly, we confirmed that three genes were transcriptionally silenced in UC patient samples by qRT-PCR, suggesting that their silencing is correlated with the promoter hypermethylation. Pathway analyses were performed using GO and KEGG databases with differentially hypermethylated genes in UC. Our results highlight that aberrant hypermethylation was identified in UC patients which can be a potential biomarker for detecting UC. Moreover, pathway-enriched hypermethylated genes are possibly implicating important cellular function in the pathogenesis of UC. Overall, this study describes a newly hypermethylated gene panel in UC patients and provides new clinical information that can be used for the diagnosis and therapeutic treatment of IBD.</P>
1.5kW급 PEMFC용 연료처리장치 내 수성가스치환반응기 시동시간 단축을 위한 수치해석
김근수(Keunsoo Kim),김선영(Sunyoung Kim),강인용(Inyong Kang),지현진(Hyunjin Ji),김영철(Youngchul Kim),배중면(Joongmyeon Bae) 대한기계학회 2011 대한기계학회 춘추학술대회 Vol.2011 No.10
A Proton Exchange Membrane Fuel Cell (PEMFC) system is spotlighted as a military power source, which has many benefits such as mobility, efficiency and quietness. PEMFC requires pure hydrogen as a fuel and on-board reforming is a realistic way to supply hydrogen. For that purpose fuel processor was developed, but is difficult to apply in real applications due to its relatively long start-up time. Two step Water Gas Shift(WGS) reactors consisting of high and low temperature reactors (HTS and LTS, respectively) mostly delay start-up time. The objective of present study is to develop and apply computational models and to design start-up protocol of WGS reactors. Transient temperature analysis was performed in each reactor with various boundary conditions. The start-up time highly depends on the wall condition and heat supply rate to WGS reactors. The start-up time is decreased with high heat supply rate. The temperature of the HTS reaches to the target very fast with the isothermal wall conditions, but the adiabatic wall condition is better for heating LTS. The optimized start-up protocol is suggested considering the results.
Yamaji, Daisuke,Kang, Keunsoo,Robinson, Gertraud W.,Hennighausen, Lothar Oxford University Press 2013 Nucleic acids research Vol.41 No.3
<P>The transcription factors Signal Transducer and Activator of Transcription (STAT) 5A/B mediate prolactin-induced mammary development during pregnancy. However, it is not clear how the different processes, expansion and maturation of alveolar precursor cells and the differential induction of milk protein genes are regulated on a molecular level. We have used mouse genetics and genome-wide analyses to determine how altering concentrations of STAT5A and STAT5B impacts mammary epithelial development during pregnancy and the regulation of target genes. The presence of only a single <I>Stat5a</I> or <I>Stat5b</I> allele was sufficient for the establishment of histologically undifferentiated alveolar units and two alleles permitted the execution of a differentiation program similar to that found with all four alleles. While one copy of <I>Stat5</I> induced limited expression of target genes, two copies activated a lactation-like gene signature. Using ChIP-seq analyses on intact tissue under physiological conditions, we found that highly expressed and regulated genes were bound by STAT5 in their promoter proximal regions, whereas upstream binding had minor biological consequences. Remarkably, 80% of the genes bound by STAT5 <I>in vivo </I>were not under STAT5 control. RNA polymerase II intensity was directly proportional to STAT5 concentration only on STAT5 regulated genes providing mechanistic insight by which STAT5 activates mammary specific genes.</P>
Bang, Man Seok,Kang, Keunsoo,Lee, Jung-ju,Lee, Yea-Jin,Choi, Jin Eun,Ban, Ju Yeon,Oh, Chung-Hun 한국유전학회 2017 Genes & Genomics Vol.39 No.3
<P>Lung cancer can be classified into two different types, non-small cell lung cancer (NSCLC) and small cell lung cancer. Up to 85% of lung cancer cases are NSCLC. To identify prognostic marker genes for NSCLC, we conducted 10 pairs of genetically matched transcriptome (NSCLC and adjacent normal tissues obtained from 10 patients) analysis using next-generation sequencing. Pathway analysis revealed that the genes associated with the cell cycle are highly upregulated in NSCLC. Integrative analysis of two independent NSCLC studies, 71 pairs (GSE40419) and 58 pairs (TCGA-LUAD), also confirmed that cell cycle-related genes are mostly upregulated in NSCLC. All three independent NSCLC transcriptomes concordantly identified 10 potential tumor-marker genes that are highly expressed as well as significantly altered in NSCLC. A quantitative real-time polymerase chain reaction experiment validated the altered expressions of the genes. Among them, downregulation of MFAP4 and AGER and upregulation of SPP1 genes in NSCLC compared to normal tissues were significantly associated with poor prognosis as evaluated by Kaplan-Meier survival and receiver operating characteristic analyses. A further analysis indicated that the expression ratio of MFAP4 and SPP1 or AGER and SPP1 can be used as potential prognostic marker genes for NSCLC.</P>
Jeena, M. T.,Jeong, Keunsoo,Go, Eun Min,Cho, Yuri,Lee, Seokyung,Jin, Seongeon,Hwang, Suk-Won,Jang, Joo Hee,Kang, Chi Soo,Bang, Woo-Young,Lee, Eunji,Kwak, Sang Kyu,Kim, Sehoon,Ryu, Ja-Hyoung American Chemical Society 2019 ACS NANO Vol.13 No.10
<P>Self-assembly of peptides containing both <SMALL>L</SMALL>- and <SMALL>D</SMALL>-isomers often results in nanostructures with enhanced properties compared to their enantiomeric analogues, such as faster kinetics of formation, higher mechanical strength, and enzymatic stability. However, occurrence and consequences of the heterochiral assembly in the cellular microenvironment are unknown. In this study, we monitored heterochiral assembly of amphiphilic peptides inside the cell, specifically mitochondria of cancer cells, resulting in nanostructures with refined morphological and biological properties owing to the superior interaction between the backbones of opposite chirality. We have designed a mitochondria penetrating tripeptide containing a diphenyl alanine building unit, named as Mito-FF due to their mitochondria targeting ability. The short peptide amphiphile, Mito-FF co-assembled with its mirror pair, Mito-ff, induced superfibrils of around 100 nm in diameter and 0.5-1 μm in length, while enantiomers formed only narrow fibers of 10 nm in diameter. The co-administration of Mito-FF and Mito-ff in the cell induced drastic mitochondrial disruption both <I>in vitro</I> and <I>in vivo</I>. The experimental and theoretical analyses revealed that pyrene capping played a major role in inducing superfibril morphology upon the co-assembly of racemic peptides. This work shows the impact of chirality control over the peptide self-assembly inside the biological system, thus showing a potent strategy for fabricating promising peptide biomaterials by considering chirality as a design modality.</P> [FIG OMISSION]</BR>
Ryu, Soo Hee,Kang, Keunsoo,Yoo, Taekyung,Joe, Cheol O.,Chung, Jae Hoon Elsevier 2011 Experimental Gerontology Vol.46 No.10
<P><B>Abstract</B></P><P>In order to better characterize epigenetic alterations at repetitive DNA elements with aging, DNA methylation and histone marks at various repeat classes were investigated. Repetitive DNA elements were hypermethylated in the brains of old mice. Histone hypoacetylation and altered histone trimethylation at repetitive sequences were detected in brain tissues during aging. The expression of repeat-derived transcripts (RDTs) was then measured to explore any correlations with the observed epigenetic alterations. Large numbers of RDTs investigated were down-regulated along with age. Bisulfite sequencing revealed that CpG dinucleotide methylation patterns at the repeats of the RDT promoter region were mostly well maintained during aging. ChIP assay showed that histones were deacetylated at the promoter region of RDTs in aged mice brain. The observations indicate that the transcriptional repression of RDTs appears to be related to histone hypoacetylation, but not to DNA hypermethylation at repeat DNA elements in the brains of aged mice.</P> <P><B>Highlights</B></P><P>► Poly(A)-binding protein (Pabp) is in a complex with Bic-D. ► <I>pabp</I> interacts genetically with <I>Bic-D</I> and <I>osk. ► pabp</I> is essential for oocyte growth, and for stability and localization of <I>osk</I>. ► Pabp binds specifically to A-rich sequences (ARS) in the <I>osk</I> 3′UTR. ► <I>osk</I> 3′UTR ARS are required <I>in vivo</I> for <I>osk</I> function during early oogenesis.</P>