• Molecules and Cells
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• v.22 no.2
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• pp.163-167
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• 2006

Histone deacetylase (HDAC) activity is commonly associated with transcriptional repression. However, there is also evidence for a function in transcriptional activation. Previous studies have demonstrated a fundamental role of deacetylase activity in $IFN{\alpha}$-responsive gene transcription. In the case of type II IFN ($IFN{\gamma}$) results are controversial: some genes require HDAC activity, while transcription of others is repressed by HDAC. To investigate the effect of HDAC on transcription of an $IFN{\gamma}$-activated gene, real-time PCR was used to measure CXCL10 mRNA in Hela cells stimulated with $IFN{\gamma}$ in the presence or absence of the HDAC inhibitor TSA. Chromatin imunoprecipitation combined with real-time PCR was used to check acetylation of histone H4 and recruitment of the STAT1 complex to the ISRE locus of the CXCL10 gene. Activation of CXCL10 transcription in response to $IFN{\gamma}$ was paralleled by a decrease in histone H4 acetylation and an increase in recruitment of the STAT1 complex to the CXCL10 ISRE locus. The transcription of CXCL10 and histone H4 deacetylation were blocked by TSA, but the latter had no obvious affect on recruitment of the STAT1 complex. Our data indicate that $IFN{\gamma}$ and STAT-dependent gene transcription requires the participation of HDAC, as does the $IFN{\alpha}$-STAT pathway.

• Korean Journal of Microbiology
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• v.45 no.4
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• pp.312-317
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• 2009

Genome analysis of a model filamentous fungus, Aspergillus nidulans, revealed that there are six putative forkhead genes. Among them, fkhF (AN8949.2) showed A. nidulans-specific. fkhF gene is located in chromosome VII and composed of 2,337 bp coding region for 778 amino acid. Since little is known about the involvement of the forkhead proteins in the developmental process of the filamentous fungi, including A. nidulans, we generated a deletion mutant of fkhF gene and analyzed. Deletion of fkhF resulted in less-dense conidiophore formation in a solid culture. However, the sexual developmental process or cleistothecia formation was normal. Furthermore, fkhF deletion mutant produced conidiophores and conidia under the submerged culture, suggesting that the fkhF gene is involved in repression of inappropriated induction and maturation of asexual developmental process but not in sexual development.

• Molecules and Cells
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• v.21 no.2
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• pp.261-268
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• 2006

The Drosophila methuselah (mth) mutant has an approximately 35 percent increase in average lifespan, and enhanced resistance to various forms of stress, including starvation, high temperature, and dietary paraquat. To examine the transcriptional regulation of mth, we used luciferase assays employing Drosophila S2 cells. Two positive control elements were found at -542 ~ -272 (PE1) and +28 ~ +217 (PE2), where putative binding sites for transcription factors including Dorsal (Dl) were identified. Cotransfection of a Dl expression plasmid with a mth-luciferase reporter plasmid resulted in decreased reporter activity. PE1 and PE2, the minimal elements for strong promoter activity, were required for maximal repression by Dl protein. The N-terminal Rel homology domain (RHD) of Dl was not sufficient for repression of mth. We demonstrated by chromatin affinity precipitation (ChAP) assays in S2 cells that Dl bound to the putative PE1 binding site. Unexpectedly, semi-quantitative RT-PCR analysis revealed that the level of mth transcripts was reduced in dl flies. However, the in vivo result support the view that mth expression is regulated by dl, since it is well known that Dl functions as both a transcriptional activator and repressor depending on what other transcription factors are present. These findings suggest that both innate immunity and resistance to stress are controlled by Dl protein.

• Journal of Microbiology and Biotechnology
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• v.31 no.5
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• pp.659-666
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• 2021

After Candida albicans, Candida glabrata is one of the most common fungal species associated with candidemia in nosocomial infections. Rapid acquisition of nutrients from the host is important for the survival of pathogens which possess the metabolic flexibility to assimilate different carbon and nitrogen compounds. In Saccharomyces cerevisiae, nitrogen assimilation is controlled through a mechanism known as Nitrogen Catabolite Repression (NCR). NCR is coordinated by the action of four GATA factors; two positive regulators, Gat1 and Gln3, and two negative regulators, Gzf3 and Dal80. A mechanism in C. glabrata similar to NCR in S. cerevisiae has not been broadly studied. We previously showed that in C. glabrata, Gln3, and not Gat1, has a major role in nitrogen assimilation as opposed to what has been observed in S. cerevisiae in which both factors regulate NCR-sensitive genes. Here, we expand the knowledge about the role of Gln3 from C. glabrata through the transcriptional analysis of BG14 and gln3Δ strains. Approximately, 53.5% of the detected genes were differentially expressed (DEG). From these DEG, amino acid metabolism and ABC transporters were two of the most enriched KEGG categories in our analysis (Up-DEG and Down-DEG, respectively). Furthermore, a positive role of Gln3 in AAA assimilation was described, as was its role in the transcriptional regulation of ARO8. Finally, an unexpected negative role of Gln3 in the gene regulation of ABC transporters CDR1 and CDR2 and its associated transcriptional regulator PDR1 was found. This observation was confirmed by a decreased susceptibility of the gln3Δ strain to fluconazole.

• Molecular Medicine Reports
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• v.20 no.3
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• pp.2339-2346
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• 2019

Reactive oxygen species (ROS) are important cellular second messengers involved in various aspects of cell signaling. ROS are elevated in multiple types of cancer cells, and this elevation is known to be involved in pathological processes of cancer. Although high levels of ROS exert cytotoxic effects on cancer cells, low levels of ROS stimulate cell proliferation and survival by inducing several pro-survival signaling pathways. In addition, ROS have been shown to induce epithelial-mesenchymal transition (EMT), which is essential for the initiation of metastasis. However, the precise mechanism of ROS-induced EMT remains to be elucidated. In the present study, it was indicated that ROS induce EMT by activating Snail expression, which then represses E- cadherin expression in MCF-7 cells. It was further indicated that distal-less homeobox-2 (Dlx-2), one of the human Dlx gene family proteins involved in embryonic development, acts as an upstream regulator of ROS-induced Snail expression. It was also revealed that ROS treatment induces the glycolytic switch, a phenomenon whereby cancer cells primarily rely on glycolysis instead of mitochondrial oxidative phosphorylation for ATP production, even in the presence of oxygen. In addition, ROS inhibited oxidative phosphorylation and caused cytochrome c oxidase inhibition via the Dlx-2/Snail cascade. These results suggest that ROS induce EMT, the glycolytic switch and mitochondrial repression by activating the Dlx-2/Snail axis, thereby playing crucial roles in MCF-7 cancer cell progression.

• KSBB Journal
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• v.13 no.3
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• pp.325-330
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• 1998

The methylotrophic yeast, Pichia pastoris, is known to be a potential host to offer many advantages for production of recombinant proteins. Fermentation parameters were optimized to enhance the heterologous ${\beta}$-galactosidase productivity with P. pastoris. Optimum concentration of methanol, used as inducer, was observed to be 8 g/L and the extent of repression of AOX1 promoter by glycerol was lower than by glucose. The degradation of the gene product ${\beta}$-galactosidase by protease was inhibited as the pH increased from 5 to 8 and the yeast extract(1%) as nitrogen source increased expression level 4 times higher compared to yeast nitrogen base(1%) as nitrogen source increased expression level 4 times higher compared to yeast nitrogen base(1%). Induction method, in which methanol is just added to fermentation medium without centrifugation, was found to be as much effective as the one with centrifugation.

• BMB Reports
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• v.42 no.3
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• pp.154-159
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• 2009

JARID1B (jumonji AT rich interactive domain 1B) is a large nuclear protein that is highly expressed in breast cancers and is proposed to function as a repressor of gene expression. In this paper, a phage display screen using the N-terminus of JARID1B as bait identified one of the JARID1B interacting proteins, namely PcG protein (Polycomb group) hPc2. We demonstrated that the C-terminal region, including the COOH box, was required for the interaction with the N-terminus of JARID1B. In a reporter assay system, co-expression of JARID1B with hPc2 significantly enhanced the transcriptional repression. These results support a role for hPc2 acting as a transcriptional co-repressor.

• Journal of Life Science
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• v.17 no.4 s.84
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• pp.593-598
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• 2007

Amino acids of histone tail are covalently modified in eukaryotic cells. Lysine residues in histone H3 and H4 are methylated at three levels; mono-, di- or trimethylation. Methylation in histones is related with transcription of the genes in distinct pattern depending on lysine residues and methylated levels. Relation between transcription and methylation has been relatively well understood at three lysines H3K4, H3K9 and H3K36. H3K4 is methylated in active or potentially active chromatin and its methylation associates with active transcription. H3K9 is generally methylated in heterochromatin or repressed gene, but trimethylation of this lysine occur in actively transcribed genes also. Methylation at H3K36 generally correlates with active chromatin/transcription, but the correlation of its dimethylation with transcription is controversial. All together methylation patterns of individual lysine residues in histone relate with activation or repression of transcription and may provide distinctive roles in transcriptional regulation of the eukaryotic genes.

• Molecules and Cells
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• v.26 no.3
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• pp.217-227
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• 2008

Heterochromatin protein 1 (HP1) was first described in Drosophila melanogaster as a heterochromatin associated protein with dose-dependent effect on gene silencing. The HP1 family is evolutionarily highly conserved and there are multiple members within the same species. The multi-functionality of HP1 reflects its ability to interact with diverse nuclear proteins, ranging from histones and transcriptional co-repressors to cohesion and DNA replication factors. As its name suggests, HP1 is well-known as a silencing protein found at pericentromeres and telomeres. In contrast to previous views that heterochromatin is transcriptionally inactive; noncoding RNAs transcribed from heterochromatic DNA repeats regulates the assembly and function of heterochromatin ranging from fission yeast to animals. Moreover, more recent progress has shed light on the paradoxical properties of HP1 in the nucleus and has revealed, unexpectedly, its existence in the euchromatin. Therefore, HP1 proteins might participate in both transcription repression in heterochromatin and euchromatin.

• Journal of Microbiology and Biotechnology
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• v.17 no.2
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• pp.187-194
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• 2007

In order to utilize different nitrogen sources and to survive in a situation of nitrogen limitation, microorganisms have developed sophisticated mechanisms to adapt their metabolism to a changing nitrogen supply. In this communication, the recent knowledge of nitrogen regulation in the amino acid producer Corynebacterium glutamicum is summarized. The core adaptations of C. glutamicum to nitrogen limitation on the level of transcription are controlled by the global regulator AmtR. Further components of the signal pathway are GlnK, a $P_{II}-type$ signal transduction protein, and GlnD. Mechanisms involved in nitrogen control in C. glutamicum regulating gene expression and protein activity are repression of transcription, protein-complex formation, protein modification by adenylylation, change of intracellular localization, and proteolysis.