• Genomics & Informatics
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• v.4 no.3
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• pp.97-102
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• 2006

In acute leukemia patients, several successful methods of expression profiling have been used for various purposes, i.e., to identify new disease class, to select a therapeutic target, or to predict chemo-sensitivity and clinical outcome. In the present study, we tested the peripheral blood of 47 acute leukemia patients in an attempt to identify differentially expressed genes in AML and ALL using a Korean-made 10K oligo-nucleotide microarray. Methods: Total RNA was prepared from peripheral blood and amplified for microarray experimentation. SAM (significant analysis of microarray) and PAM (prediction analysis of microarray) were used to select significant genes. The selected genes were tested for in a test group, independently of the training group. Results: We identified 345 differentially expressed genes that differentiated AML and ALL patients (FWER<0.05). Genes were selected using the training group (n=35) and tested for in the test group (n=12). Both training group and test group discriminated AML and ALL patients accurately. Genes that showed relatively high expression in AML patients were deoxynucleotidyl transferase, pre-B lymphocyte gene 3, B-cell linker, CD9 antigen, lymphoid enhancer-binding factor 1, CD79B antigen, and early B-cell factor. Genes highly expressed in ALL patients were annexin A 1, amyloid beta (A4) precursor protein, amyloid beta (A4) precursor-like protein 2, cathepsin C, lysozyme (renal amyloidosis), myeloperoxidase, and hematopoietic prostaglandin D2 synthase. Conclusion: This study provided genome wide molecular signatures of Korean acute leukemia patients, which clearly identify AML and ALL. Given with other reported signatures, these molecular signatures provide a means of achieving a molecular diagnosis in Korean acute leukemia patents.

• YAKHAK HOEJI
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• v.49 no.3
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• pp.205-211
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• 2005

The 3' UTR (3' untranslated region) plays important roles in controlling gene expression through regulating 3' polyadenylation, mRNA export, subcellular localization, translational efficiency, and mRNA stability. Changes in the 3' UTR sequence in an expressed transcript can result in functional changes of the genes that are expressed in pathological conditions compared with those genes expressed in normal physiologic conditions. A genome-wide survey of 3' UTR variation was performed for the genes expressed during hematopoietic differentiation from CD34+ stem/progenitor cells to CD 15 + myeloid progenitor cells. Wide-spread differential usage of the 3' UTR was observed from the genes expressed during this cellular transition. This study implies that the 3' UTR can be a highly coordinated region for post-transcriptional regulation of the function of expressed genes.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.13-16
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• 2000

Microorganisms have been widely employed for the production of useful bioproducts including primary metabolites such as ethanol, succinic acid, acetone and butanol, secondary metabolites represented by antibiotics, proteins, polysaccharides, lipids and many others. Since these products can be obtained in small quantities under natural condition, mutation and selection processes have been employed for the improvement of strains. Recently, metabolic engineering strategies have been employed for more efficient production of these bioproducts. Metabolic engineering can be defined as purposeful modification of cellular metabolic pathways by introducing new pathways, deleting or modifying the existing pathways for the enhanced production of a desired product or modified/new product, degradation of xenobiotics, and utilization of inexpensive raw materials. Metabolic flux analysis and metabolic control analysis along with recombinant DNA techniques are three important components in designing optimized metabolic pathways, This powerful technology is being further improved by the genomics, proteomics, metabolomics and bioinformatics. Complete genome sequences are providing us with the possibility of addressing complex biological questions including metabolic control, regulation and flux. In silico analysis of microbial metabolic pathways is possible from the completed genome sequences. Transcriptome analysis by employing ONA chip allows us to examine the global pattern of gene expression at mRNA level. Two dimensional gel electrophoresis of cellular proteins can be used to examine the global proteome content, which provides us with the information on gene expression at protein level. Bioinformatics can help us to understand the results obtained with these new techniques, and further provides us with a wide range of information contained in the genome sequences. The strategies taken in our lab for the production of pharmaceutical proteins, polyhydroxyalkanoate (a family of completely biodegradable polymer), succinic acid and me chemicals by employing metabolic engineering powered by genomics, proteomics, metabolomics and bioinformatics will be presented.

• BMB Reports
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• v.37 no.1
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• pp.107-113
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• 2004

Since the completion of the genome project of the nematode C. elegans in 1998, functional genomic approaches have been applied to elucidate the gene and protein networks in this model organism. The recent completion of the whole genome of C. briggsae, a close sister species of C. elegans, now makes it possible to employ the comparative genomic approaches for identifying regulatory mechanisms that are conserved in these species and to make more precise annotation of the predicted genes. RNA interference (RNAi) screenings in C. elegans have been performed to screen the whole genome for the genes whose mutations give rise to specific phenotypes of interest. RNAi screens can also be used to identify genes that act genetically together with a gene of interest. Microarray experiments have been very useful in identifying genes that exhibit co-regulated expression profiles in given genetic or environmental conditions. Proteomic approaches also can be applied to the nematode, just as in other species whose genomes are known. With all these functional genomic tools, genetics will still remain an important tool for gene function studies in the post genome era. New breakthroughs in C. elegans biology, such as establishing a feasible gene knockout method, immortalized cell lines, or identifying viruses that can be used as vectors for introducing exogenous gene constructs into the worms, will augment the usage of this small organism for genome-wide biology.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.205-210
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• 2008

Recent studies suggest that activated microglial cells play an essential role in the inflammatory responses and neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This study was conducted to evaluate the protective mechanisms of Asiasarum sieboldi (AS) on LPS-induced activation of BV-2 microglial cells. The effects of AS on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7$/mL) for 24 h and then pretreated with 1 ${\mu}g$/mL AS or left untreated for 30 min. Next, 1 ${\mu}g$/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min and 1 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AS. The microarray analysis revealed that MAPK signaling pathway-related genes were downregulated in AS-treated BV-2 microglial cells. AS can affect the neuroinflammatory-related pathway such as MAPK signaling pathway in activated BV-2 microglial cells.

• Journal of Microbiology and Biotechnology
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• v.19 no.2
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• pp.208-214
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• 2009

Steroid hormones have long been known to have a profound influence on the immune system. Although the functions of the nuclear receptors in the development of T cells are fairly well studied, the differential expression of these receptors in T helper cells is poorly understood. Here, we investigated the differential expression of nuclear receptors and coregulators in Th1 and Th2 cells by genome-wide micro array analysis. The result showed that several nuclear receptors and coregulators are differentially expressed in these cells. The result was confirmed by RT-PCR. The result showed that $RXR{\alpha}$ is highly expressed in Th2 cells. Overexpression of $RXR{\alpha}$ in a Jurkat human T cell line induced IL4 but not IFN-${\gamma}$ gene expression, suggesting that $RXR{\alpha}$ plays a selective role in Th1 and Th2 differentiation. In summary, these results suggest that Th1/Th2 differentiation is influenced by differential regulation of nuclear receptors and coregulators.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.1-6
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• 2009

Microglial cells constitute the first line of defense against infection and injury in the brain. This study was conducted to evaluate the protective mechanisms of Agrimonia pilosa (AP) on LPS-induced activation of BV-2 microglial cells. The effects of AP on gene expression profiles in activated BV-2 microglial cells were evaluated using microarray analysis. BV-2 microglial cells were cultured in a 100 mm dish ($1{\times}10^7/mL$) for 24 hr and then pretreated with 1 g/mL AP or left untreated for 30 min. Next, 1 g/mL LPS was added to the samples and the cells were reincubated at $37^{\circ}C$ for 30 min, 3 hr and 6 hr. The gene expression profiles of the BV-2 microglial cells varied depending on the AP. The microarray analysis revealed that MAPK signaling pathway-related genes were down-regulated and IL10 gene was up-regulated in AP-treated BV-2 microglial cells. AP can affect the inflammatory response and MAPK pathway in BV-2 microglial cells.

• BMB Reports
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• v.49 no.10
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• pp.578-583
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• 2016

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.59-60
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• 2000

The past few years have seen a dramatic increase in gene expression data on the basis of DNA microarrays or DNA chips. Going beyond a generic view on the genome, microarray data are able to distinguish between gene populations in different tissues of the same organism and in different states of cells belonging to the same tissue. This affords a cell-wide view of the metabolic and regulatory processes under different conditions, building an effective basis for new diagnoses and therapies of diseases. In this talk we present machine learning techniques for effective mining of DNA microarray data. A brief introduction to the research field of machine learning from the computer science and artificial intelligence point of view is followed by a review of recently-developed learning algorithms applied to the analysis of DNA chip gene expression data. Emphasis is put on graphical models, such as Bayesian networks, latent variable models, and generative topographic mapping. Finally, we report on our own results of applying these learning methods to two important problems: the identification of cell cycle-regulated genes and the discovery of cancer classes by gene expression monitoring. The data sets are provided by the competition CAMDA-2000, the Critical Assessment of Techniques for Microarray Data Mining.

• BMB Reports
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• v.50 no.4
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• pp.162-163
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• 2017

RNA polymerase II-interacting the Set2 methyltransferase co-transcriptionally methylates histone H3 at lysine 36 within the body of genes. This modification facilitates histone deacetylation by Rpd3S HDAC in 3' transcribed regions to suppress cryptic initiation and slow elongation. Although this pathway is important for global deacetylation, no strong effects have been seen on genome-wide transcription under optimized laboratory conditions. In contrast, this pathway slows the kinetics of mRNA induction when target genes are induced upon environmental changes. Interestingly, a majority of Set2-repressed genes are overlapped by a lncRNA transcription that targets H3K36 methylation and deacetylation by Rpd3S HDAC to mRNA promoters. Furthermore, this pathway delays the induction of many cryptic transcripts upon environmental changes. Therefore, the Set2-Rpd3S HDAC pathway functions to fine-tune expression dynamics of mRNAs and ncRNAs.