• Molecules and Cells
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• v.43 no.2
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• pp.188-197
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• 2020

Cells are designed to be sensitive to a myriad of external cues so they can fulfil their individual destiny as part of the greater whole. A number of well-characterised signalling pathways dictate the cell's response to the external environment and incoming messages. In healthy, well-ordered homeostatic systems these signals are tightly controlled and kept in balance. However, given their powerful control over cell fate, these pathways, and the transcriptional machinery they orchestrate, are frequently hijacked during the development of neoplastic disease. A prime example is the Wnt signalling pathway that can be modulated by a variety of ligands and inhibitors, ultimately exerting its effects through the β-catenin transcription factor and its downstream target genes. Here we focus on the interplay between the three-member family of RUNX transcription factors with the Wnt pathway and how together they can influence cell behaviour and contribute to cancer development. In a recurring theme with other signalling systems, the RUNX genes and the Wnt pathway appear to operate within a series of feedback loops. RUNX genes are capable of directly and indirectly regulating different elements of the Wnt pathway to either strengthen or inhibit the signal. Equally, β-catenin and its transcriptional co-factors can control RUNX gene expression and together they can collaborate to regulate a large number of third party co-target genes.

• KSBB Journal
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• v.19 no.4
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• pp.308-314
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• 2004

A degenerate set of PCR primers based on two conserved regions (heme binding region and oxygen ligand pocket) were designed and successfully applied to amplify DNA fragments of cytochrome P450 hydroxylase (CYP) genes from a rare actinomycetes, S. benihana. The PCR amplified products were employed as a DNA probe to clone the entire CYP genes from S. benihana genomic library. Five different CYP-positive cosmids were isolated by colony hybridization as well as PCR confirmation. The complete nucleotide sequencing of five different CYP genes revealed that each unique CYP showed a significant amino acid homology to previously-known CYP genes involved in streptomycetes secondary metabolism. In addition, four CYP genes (CYP502, CYP503, CYP504, CYP506) were found to be linked to ferredoxin genes in the chromosome, and the CYP503 gene showed the high degree of amino acid similarity to the previously well-characterized CYP105 family in streptomycetes.

• Clinical and Experimental Reproductive Medicine
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• v.39 no.2
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• pp.87-93
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• 2012

Objective: Lin28 has been known to control the proliferation and pluripotency of embryonic stem cells. The purpose of this study was to determine the downstream effectors of Lin28 in mouse embryonic stem cells (mESCs) by RNA interference and microarray analysis. Methods: The control siRNA and Lin28 siRNA (Dharmacon) were transfected into mESCs. Total RNA was prepared from each type of transfected mESC and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis to confirm the downregulation of Lin28. The RNAs were labeled and hybridized with an Affymetrix Gene-Chip Mouse Genome 430 2.0 array. The data analysis was accomplished by GenPlex 3.0 software. The expression levels of selected genes were confirmed by quantitative real-time RT-PCR. Results: According to the statistical analysis of the cDNA microarray, a total of 500 genes were altered in Lin28-downregulated mESCs (up-regulated, 384; down-regulated, 116). After differentially expressed gene filtering, 31 genes were selected as candidate genes regulated by Lin28 downregulation. Among them, neuropeptide Y5 receptor and oocyte-specific homeobox 5 genes were significantly upregulated in Lin28-downregulated mESCs. We also showed that the families of neuropeptide Y receptor (Npyr) and oocyte-specific homeobox (Obox) genes were upregulated by downregulation of Lin28. Conclusion: Based on the results of this study, we suggest that Lin28 controls the characteristics of mESCs through the regulation of effectors such as the Npyr and Obox families.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6631-6636
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• 2013

Through years of effort, researchers have made notable progress in gene and microRNA fields about retinoblastoma morbidity. However, experimentally validated data for genes, microRNAs (miRNAs) and transcription factors (TFs) can only be found in a scattered form, which makes it difficult to conclude the relationship between genes and retinoblastoma systematically. In this study, we regarded genes, miRNAs and TFs as elements in the regulatory network and focused on the relationship between pairs of examples. In this way, we paid attention to all the elements macroscopically, instead of only researching one or several. To show regulatory relationships over genes, miRNAs and TFs clearly, we constructed 3 regulatory networks hierarchically, including a differentially expressed network, a related network and a global network, for analysis of similarities and comparison of differences. After construction of the three networks, important pathways were highlighted. We constructed an upstream and downstream element table of differentially expressed genes and miRNAs, in which we found self-adaption relations and circle-regulation. Our study systematically assessed factors in the pathogenesis of retinoblastoma and provided theoretical foundations for gene therapy researchers. In future studies, especial attention should be paid to the highlighted genes and miRNAs.

• 한국균학회소식:학술대회논문집
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• 2015.11a
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• pp.28-28
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• 2015

Asexual reproduction or conidiation in aspergilli is a primary mean to produce their progenies that is environmentally and genetically controlled tightly. Previously, intensive researches in the model fungus Aspergillus nidulans disclosed some genes playing important roles in asexual and sexual development. Among them, one gene encoding a putative helix-loop-helix (HLH) transcription factor, named ndrA, has been isolated and characterized as a downstream regulator of developmental master regulator NsdD. By using comparative genome search of A. niduans NdrA protein, its orthologues have been identified in A. fumigatus and A. flavus, respectively (AfudrnA and AfldrnA). Deletion of the ndrA genes in both Aspergillus species made them unable to produce the conidia yet abundant production of sclerotia in A. flavus. Complementation of ndrA deletion strains by intact ndrA ORFs has restored the conidiation as in the control strains. In A. fumigatus, ndrA deletion also resulted in loss of conidiation phenotype. Northern analyses showed that the ndrA genes in both Aspergillus species are highly expressed at the early stage of the conidiation. Interestingly, the ndrA genes were found to be necessary for the proper expression of brlA genes. Antifungal sensitivity test revealed that the ndrA genes might be responsible for the sensitivity or resistance to some antifungal agents. However, ndrA deletion did not greatly influence the growth in both strains. And the A. flavus ndrA gene did not affect the aflatoxin production. Taken together, ndrA genes in Aspergillus species could be an important positive regulator of conidiation under the regulation of the nsdD gene yet upstream of the brlA gene.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.49-52
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• 2008

Parkinson's disease is characterized by motor disturbances and dopaminergic neurodegeneration. parkin and PINK1, two most critical Parkinson's disease-associated genes, have been intensively studied to address the underlying molecular pathogenesis of the disease, but our understanding still remains unclear. Through generation and characterization of Drosophila mutants for PINK1, we show that PINK1 is required for mitochondrial integrity and function in both indirect flight muscles and dopaminergic neurons. Surprisingly, we find that PINK1 mutants share striking phenotypic similarities with parkin mutants. Indeed, transgenic expression of parkin dramatically ameliorates all PINK1 loss-of-function phenotypes, but not vice versa, implicating that Parkin acts downstream of PINK1 in maintaining mitochondrial integrity and function in both muscles and dopaminergic neurons. With the establishment of the PINK1-Parkin pathway, we are trying to further investigate the detailed molecular relationship between PINK1 and Parkin using both mammalian dopaminergic neuronal cells for biochemical analysis and Drosophila model animal for genetic analysis. We believe that elucidating the molecular function of Parkinson's disease-associated genes will be of big help for the ultimate understanding of the pathogenic mechanism of this disease and also for the development of effective drugs for Parkinson's disease.

• Molecules and Cells
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• v.24 no.3
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• pp.394-408
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• 2007

Several genes/QTLs governing resistance/tolerance to abiotic and biotic stresses have been reported and mapped in rice. A QTL for submergence tolerance was found to be co-located with a major QTL for broad-spectrum bacterial leaf blight (bs-blb) resistance on the long arm of chromosome 5 in indica cultivars FR13A and IET8585. Using the Nipponbare (japonica) and 93-11 (indica) genome sequences, we identified, in silico, candidate genes in the chromosomal region [Kottapalli et al. (2006)]. Transcriptional profiling of FR13A and IET8585 using a rice 22K oligo array validated the above findings. Based on in silico analysis and arraying we observed that both cultivars respond to the above stresses through a common signaling system involving protein kinases, adenosine mono phosphate kinase, leucine rich repeat, PDZ/DHR/GLGF, and response regulator receiver protein. The combined approaches suggest that transcription factor EREBP on long arm of chromosome 5 regulates both submergence tolerance and blb resistance. Pyruvate decarboxylase and alcohol dehydrogenase, co-located in the same region, are candidate downstream genes for submergence tolerance at the seedling stage, and t-snare for bs-blb resistance. We also detected up-regulation of novel defense/stress-related genes including those encoding fumaryl aceto acetate (FAA) hydrolase, scramblase, and galactose oxidase, in response to the imposed stresses.

• Korean Journal of Microbiology
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• v.36 no.1
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• pp.1-7
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• 2000

The genes involved in riboflavin synthesis (ribI, II, III, and IV) were found immediately downstream of luxG in the lux operon from Photobacterium species. The single stranded DNA containing the intergenic region of lux genes and rib genes from Photobacterium phosphoreum was fully protected by P. phosphoreum mRNA from the S1 nuclease mapping assay suggesting that a transcriptional terminator was not present in the region. In addition, the levels of riboflavin synthase activity in P. phosphoreum was increased during the development of bacterial bioluminescence in the same fashion as the luciferase and fatty acid reductase activities. Insertion of the Photobacterium leiognathi DNA extending from luxB to ribII, between a strong lux promoter and a reporter gene (chloramphenicol acetyltransferase, CAT) and transferred by conjugation into P. leiognathi, did not affect expression of reporter gene. Moreover the CAT gene was not expressed in an analogous construct missing the lux promoter indicating that a promoter was not present in this region. Based on the data here, it can be concluded that the lux genes and rib genes in Photobacterium species are under common regulation.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.177.2-177.2
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• 2003

Thiazolidinediones (TZDs) are a new class of compound that increase insulin sensitivity in type 2 diabetic patients. Thiazolidinediones (TZDs) act as ligands for a member of the nuclear hormone receptor superfamily, peroxisome proliferator-activated receptor-$\gamma$ (PPAR-$\gamma$), which is highly expressed in fatty tissue and, moreover, has been shown to play an important role in fat cell differentiation. The strong interaction between the antidiabetic activity ofTZDs and their ability to activate PPAR-$\gamma$ suggests that PPAR-$\gamma$, through downstream-regulated genes, mediates the effects of TZDs. (omitted)

• Asian-Australasian Journal of Animal Sciences
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• v.27 no.11
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• pp.1532-1539
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• 2014

Although growth rate is one of the main economic traits of concern in pig production, there is limited knowledge on its epigenetic regulation, such as DNA methylation. In this study, we conducted methyl-CpG binding domain protein-enriched genome sequencing (MBD-seq) to compare genome-wide DNA methylation profile of small intestine and liver tissue between fast- and slow-growing weaning piglets. The genome-wide methylation pattern between the two different growing groups showed similar proportion of CpG (regions of DNA where a cytosine nucleotide occurs next to a guanine nucleotide in the linear sequence) coverage, genomic regions, and gene regions. Differentially methylated regions and genes were also identified for downstream analysis. In canonical pathway analysis using differentially methylated genes, pathways (triacylglycerol pathway, some cell cycle related pathways, and insulin receptor signaling pathway) expected to be related to growth rate were enriched in the two organ tissues. Differentially methylated genes were also organized in gene networks related to the cellular development, growth, and carbohydrate metabolism. Even though further study is required, the result of this study may contribute to the understanding of epigenetic regulation in pig growth.