• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.4
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• pp.381-385
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• 2007

Bone is a dynamic organ that bone remodeling occurs throughout life and involves the process in which the bone matrix is broken down through resorption by osteoclasts and then built back again through bone formation by osteoblasts. Usually these two processes balance each other and a stable level of bone mass is maintained. We here discuss transcription factors involved in regulating the osteoblast differentiation pathway. Runx2 is a transcription factor which is essential in skeletal development by regulating osteoblast differentiation and chondrocyte maturation. Its companion subunit, Cbf${\beta}$ is needed for an early step in osteoblast differentiation pathway. Whereas Osterix(Osx) is a new identified osteoblast-specific transcription factor which is required for the differentiation of preosteoblasts into more mature and functional osteoblasts. We also discuss other transcription factors, Msx1 and 2, Dlx5 and 6, Twist, and Sp3 that affect skeletal patterning and development. Understanding the characteristics of mice in which these transcription factors are inactivated should help define their role in bone physiology and pathology of bone defects.

• Molecules and Cells
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• v.21 no.3
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• pp.376-380
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• 2006

Gene expression is regulated in large part at the level of transcription under the control of sequence-specific transcriptional regulatory proteins. Therefore, the ability to affect gene expression at will using sequencespecific artificial transcription factors would provide researchers with a powerful tool for biotechnology research and drug discovery. Previously, we isolated 56 novel sequence-specific DNA-binding domains from the human genome by in vivo selection. We hypothesized that these domains might be more useful for regulating gene expression in higher eukaryotic cells than those selected in vitro using phage display. However, an unpredictable factor, termed the "context effect", is associated with the construction of novel zinc finger transcription factors--- DNA-binding proteins that bind specifically to 9-base pair target sequences. In this study, we directly selected active artificial zinc finger proteins from a zinc finger protein library. Direct in vivo selection of constituents of a zinc finger protein library may be an efficient method for isolating multi-finger DNA binding proteins while avoiding the context effect.

• Korean Journal of Microbiology
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• v.49 no.1
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• pp.8-16
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• 2013

A GAL4 type transcription factor gene (formally annotated as AN3912) locating downstream of sndA (AN3911) was characterized. The putative transcription factor carries both Zn(II)2Cys6 binuclear cluster DNA-binding domain and transcription activator domain. The gene named gtfA (gal4 type transcription factor) had an open reading frame which consisted of 762 amino acids and was disrupted by three introns. The deletion mutant produced reduced amount of conidia but increased amount of fruiting bodies, suggesting that the GtfA make function in decision of asexual preferential to sexual development. The forced over expression of gtfA caused the retardation of fruiting body formation on high glucose concentration. The transcript level of gtfA was kept constant through the life cycle except late vegetative stage and early sexual development stage during which slight increase was found. The expression of gtfA was not significantly affected by sexual or asexual development regulators, such as VeA, NsdD or FluG, FadA, and SfaD. The GtfA repressed the nsdC transcription, which suggested that GftA control sexual development negatively via negative regulation of nsdC expression.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.70-70
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• 2003

Estrogen receptor is a ligand-activated transcription factor. Its action depends on the receptor, its ligand, and its coactivator proteins. As a consequence, the concentration of the receptor is a major component that governs the magnitude of the estrogen response. Despite the extensive knowledge on mechanism of estrogen receptor action, regulation of estrogen receptor itself is not very well understood. Estrogen receptor is known to be downregulated under hypoxia leading to inhibition of estrogen receptor mediated transcription activation. We have studied mechanism of loss of estrogen responsiveness under hypoxia. We found that Hif-l${\alpha}$, a major transcription factor regulating hypoxic response, inhibited transcription of estrogen response element driven luciferase gene by expression of HIF-l${\alpha}$/vp16 construct designed to contain transcription activity under normoxia. This loss of estrogen responsiveness appears to be the result of ER${\alpha}$ downregulation. ER${\alpha}$was downregulated at the levels of ligand-biding and protein within l2-24h, and the response was blocked by the proteasome inhibitor MG132, protein synthesis inhibitor cyclohexamide, and tyrosine kinase inhibitor Genistein. These results demonstrate that Hif-l${\alpha}$ downregulates ER${\alpha}$ by proteasome dependent pathway.

• Animal cells and systems
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• v.7 no.3
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• pp.173-186
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• 2003

The transition metal cadmium is a serious occupational and environmental toxin. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-responsive proteins. The metal-regulatory transcription factor 1 (MTF-1) is a key regulator of heavy-metal induced transcription of metallothionein-I and II and other genes in mammals and other metazoans. Transcriptional activation of genes by MTF-1 is mediated through binding to metal-responsive elements in the target gene promoters. Phosphorylation of MTF-1 plays a critical role in the cadmium-inducible transcriptional activation of metallothionein and other responses. Studies using inhibitors indicate that multiple kinases and signal transduction cascades, including those mediated by protein kinase C, tyrosine kinase and casein kinase II, are essential for cadmium-mediated transcriptional activation. In addition, calcium signaling is also involved in regulating metal-activated transcription. In several species, cadmium induces heat shock genes. Recently much progress has been made in elucidating the cellular machinery that regulates this metal-inducible gene expression. This review summarizes these recent advances in understanding the role of some known cadmium-responsive genes and the molecular mechanisms that activate metal-responsive transcription factor, MTF-1.

• Animal cells and systems
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• v.2 no.1
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• pp.117-122
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• 1998

D-raf, a Drosophila homolog of the human c-raf-1, is known as a signal transducer in cell proliferation and differentiation. A previous study found that the D-raf gene expression is regulated by the DNA replication-related element (DRE)/DRE-binding factor (DREF) system. In this study, we found the sequences homologous to transcription factor C/EBP, MyoD, STAT and Myc recognition sites in the D-raf promoter. We have generated various base substitutional mutations in these recognition sites and subsequently examined their effects on D-raf promoter activity through transient CAT assays in Kc cells with reporter plasmids p5'-878DrafCAT carrying the mutations in these binding sites. Through gel mobility shift assay using nuclear extracts of Kc cells, we detected factors binding to these recognition sites. Our results show that transcription factor C/EBP, STAT and Myc binding sites in D-raf promoter region play a positive role in transcriptional regulation of the D-raf gene and the Myo D binding site plays a negative role.

• Journal of Life Science
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• v.18 no.10
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• pp.1348-1354
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• 2008

mi transcription factor (MITF) is important in regulating the differentiation of mast cells. In particular, MITF regulates the transcription of the mouse mast cell-specific serine protease (mMCP)-6 gene, which is generally expressed by the connective tissue-type of mast cells. In this study, we investigated alternative isoforms of MITF that regulate transcription of the mMCP-6 gene in bone marrow-derived cultured mast cells in mice. The expression of MITF isoforms was examined by RT-PCR. We observed that MITF-A, -E, -H and -Mc were expressed by mucosal-type mast cells cultured in the presence of IL-3, whereas the connective tissue-type mast cells cultured in the presence of stem cell factor (SCF) expressed MITF-A. Overexpression of MITF isoforms increased luciferase activity through the mMCP-6 promoter in NIH-3T3 cells and elevated the level of mMCP-6 expression in the MC/9 mast cell line. Moreover, mMCP-6 expression in mast cells was significantly inhibited by the depletion of MITF. The transcriptional activity and DNA binding of MITF-A was comparable to that of MITF isoforms, including MITF-E, -H, and -Mc. Our results therefore suggest that MITF-A may be an important isoform of MITF in regulating the transcription of mMCP-6 in mouse connective tissue mast cells.

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.3
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• pp.449-456
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• 2018

Objective: Nanog, a homeodomain protein, has been investigated in humans and mice using embryonic stem cells (ESCs). Because of the limited availability of ESCs, few studies have reported the function and role of Nanog in porcine ESCs. Therefore, in this study, we investigated the location of the porcine Nanog chromosome and its basal promoter activity, which might have potential applications in development of ESCs specific marker as well as understanding its operating systems in the porcine. Methods: To characterize the porcine Nanog promoter, the 5'-flanking region of Nanog was isolated from cells of mini-pig ears. BLAST database search showed that there are two porcine Nanog genomic loci, chromosome 1 and 5, both of which contain an exon with a start codon. Deletion mutants from the 5'-flanking region of both loci were measured using the Dual-Luciferase Reporter Assay System, and a fluorescence marker, green fluorescence protein. Results: Promoter activity was detected in the sequences of chromosome 5, but not in those of chromosome 1. We identified the sequences from -99 to +194 that possessed promoter activity and contained transcription factor binding sites from deletion fragment analysis. Among the transcription factor binding sites, a Sp1 was found to play a crucial role in basal promoter activity, and point mutation of this site abolished its activity, confirming its role in promoter activity. Furthermore, gel shift analysis and chromatin immunoprecipitation analysis confirmed that Sp1 transcription factor binds to the Sp1 binding site in the porcine Nanog promoter. Taken together, these results show that Sp1 transcription factor is an essential element for porcine Nanog basal activity the same as in human and mouse. Conclusion: We showed that the porcine Nanog gene is located on porcine chromosome 5 and its basal transcriptional activity is controlled by Sp1 transcription factor.

• The Plant Pathology Journal
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• v.30 no.3
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• pp.236-244
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• 2014

The plant pathogen Fusarium graminearum causes Fusarium head blight in cereal crops and produces mycotoxins that are harmful to animals and humans. For the initiation and spread of disease, asexual and sexual reproduction is required. Therefore, studies on fungal reproduction contribute to the development of new methods to control and maintain the fungal population. Screening a previously generated transcription factor mutant collection, we identified one putative $C_2H_2$ zincfinger transcription factor, pcs1, which is required for both sexual and asexual reproduction. Deleting pcs1 in F. graminearum resulted in a dramatic reduction in conidial production and a complete loss of sexual reproduction. The pathways and gene ontology of pcs1-dependent genes from microarray experiments showed that several G-protein related pathways, oxidase activity, ribosome biogenesis, and RNA binding and processing were highly enriched, suggesting that pcs1 is involved in several different biological processes. Further, overexpression of pcs1 increased conidial production and resulted in earlier maturation of ascospores compared to the wild-type strain. Additionally, the vegetative growth of the overexpression mutants was decreased in nutrient-rich conditions but was not different from the wild-type strain in nutrient-poor conditions. Overall, we discovered that the pcs1 transcription factor positively regulates both conidiation and sexual reproduction and confers nutrient condition-dependent vegetative growth.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.228.2-229
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• 2003

Estrogen Receptor is a ligand-activated transcription factor. The concentration of the receptor is a major component that regulates expression of estrogen-responsive genes. We have studied mechanism of estrogen receptor alpha (ER${\alpha}$) downregulation by HIF-1 using HIF-1${\alpha}$/VP16 constructs. ER${\alpha}$ is known to be downregulated under hypoxic condition. Transcriptional response under hypoxia is mediated through Hypoxia-inducible factor-1 (HIF-1), a transcription factor that is usullaly degraded but stabilized under hypoxia. (omitted)