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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>
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>
Zhu, Bing-Mei,Kang, Keunsoo,Yu, Ji Hoon,Chen, Weiping,Smith, Harold E.,Lee, Daeyoup,Sun, Hong-Wei,Wei, Lai,Hennighausen, Lothar Oxford University Press 2012 Nucleic acids research Vol.40 No.10
<P>Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23 827 and 111 939 STAT5A binding sites were detected in WT and STAT5A overexpressing MEFs, respectively. 13 278 and 71 561 peaks contained at least one GAS motif. 1586 and 8613 binding sites were located within 2.5 kb of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (−10 kb to +0.5 kb) was recognized by STAT5 both in WT and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes.</P>