• IMMUNE NETWORK
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• v.9 no.4
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• pp.115-121
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• 2009

Natural killer (NK) cells play key roles in innate and adaptive immune defenses. NK cell responses are mediated by two major mechanisms: the direct cytolysis of target cells, and immune regulation by production of various cytokines. Many previous reports show that the complex NK cell activation process requires de novo gene expression regulated at both transcriptional and post-transcriptional levels. Specialized un-translated regions (UTR) of mRNAs are the main mechanisms of post-transcriptional regulation. Analysis of posttranscriptional regulation is needed to clearly understand NK cell biology and, furthermore, harness the power of NK cells for therapeutic aims. This review summarizes the current understanding of mRNA metabolism during NK cell activation, focusing primarily on post-transcriptional regulation.

• Molecules and Cells
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• v.24 no.3
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• pp.307-315
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• 2007

Gene regulation is a fundamental process in biological systems, where transcription factors (TFs) play crucial roles. Inferring transcriptional interactions between TFs and their target genes has utmost importance for understanding the complex regulatory mechanisms in cellular systems. On one hand, with the rapid progress of various high-throughput experiment techniques, more and more biological data become available, which makes it possible to quantitatively study gene regulation in a systematic manner. On the other hand, transcription regulation is a complex biological process mediated by many events such as post-translational modifications, degradation, and competitive binding of multiple TFs. In this review, with a particular emphasis on computational methods, we report the recent advances of the research topics related to transcriptional regulatory networks, including how to infer transcriptional interactions, reveal combinatorial regulation mechanisms, and reconstruct TF activity profiles.

• BMB Reports
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• v.54 no.2
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• pp.89-97
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• 2021

Post-transcriptional regulation is an indispensable cellular mechanism of gene expression control that dictates various cellular functions and cell fate decisions. Recently, various chemical RNA modifications, termed the "epitranscriptome," have been proposed to play crucial roles in the regulation of post-transcriptional gene expression. To date, more than 170 RNA modifications have been identified in almost all types of RNA. As with DNA modification-mediated control of gene expression, regulation of gene expression via RNA modification is also accomplished by three groups of proteins: writers, readers, and erasers. Several emerging studies have revealed that dysregulation in RNA modification is closely associated with tumorigenesis. Notably, the molecular outcomes of specific RNA modifications often have opposite cellular consequences. In this review, we highlight the current progress in the elucidation of the mechanisms of cancer development due to chemical modifications of various RNA species.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2001.10a
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• pp.45-60
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• 2001

. Mediator of transcriptional regulation is the evolutionary conserved coactivator complex that plays He central role in the integration and recruitment of diverse regulatory signals and transcription machinery to certain promoters. In yeast, each Mediator subunit is required for transcriptional regulation of a distinct group of genes. In order to decipher the mechanistic roles of Mediator proteins in regulating developmental specific gene expression, we isolated, and analyzed a multiprotein complex containing Drosophila Mediate. homologs (dMediato.). dMediato. interacts with several sequence-sperific transcription factors and basal transcription machinery, and is critical for activated transcription in response to diverse transcriptional activators. In order to elucidate the function of Mediator in metazoan development, we isolated mutants of a conserved Mediate. subunit, Drosophila Med6 (dMed6). dMed6 null homozygotes failed to pupate and died in the third larval instar. Larval mitotic cells and most imaginal discs showed severe defects in proliferation, but no apparent morphological defect was observed in other larval tissues. Clonal analysis of dMed6 mutant cells revealed that dMed6 is essential for cell viability and proliferation of most adult cell types. Drosophila cDNA microarray, quantitative RT-PCR, and in situ expression analyses of developmentally regulated genes in dMed6 mutants showed that transcriptional activation of a subset of genes involved in neuroblast proliferation in the larval brain were most affected. Our results suggest that dMed6 is required in most for transcriptional regulation of a subset of genes important for cell proliferation and metabolism.

• BMB Reports
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• v.52 no.2
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• pp.127-132
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• 2019

Cells must fine-tune their gene expression programs for optimal cellular activities in their natural growth conditions. Transcriptional memory, a unique transcriptional response, plays a pivotal role in faster reactivation of genes upon environmental changes, and is facilitated if genes were previously in an active state. Hyper-activation of gene expression by transcriptional memory is critical for cellular differentiation, development, and adaptation. TREM (Transcriptional REpression Memory), a distinct type of transcriptional memory, promoting hyper-repression of unnecessary genes, upon environmental changes has been recently reported. These two transcriptional responses may optimize specific gene expression patterns, in rapidly changing environments. Emerging evidence suggests that they are also critical for immune responses. In addition to memory B and T cells, innate immune cells are transcriptionally hyperactivated by restimulation, with the same or different pathogens known as trained immunity. In this review, we briefly summarize recent progress in chromatin-based regulation of transcriptional memory, and its potential role in immune responses.

• BMB Reports
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• v.40 no.4
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• pp.547-553
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• 2007

Many motifs along the 1.2 kb myostatin promoter (MSTNpro) in sheep have been found by the MatInspecter program in our recent study. To further verify the role of the motifs and better understand the transcriptional regulation mechanism of the myostatin gene in sheep, the reporter gene EGFP (enhanced green fluorescent protein) was selected and the wild-type (W) vector MSTNPro$^W$-EGFP or motif-mutational (M) vector MSTNPro$^M$-EGFP were constructed. The transcriptional regulation activities were analyzed by detecting the fluorescence strength of EGFP in C2C12 myoblasts transfected with the vectors. The results showed that E-box (E) 3, E4, E5 and E7, particularly E3, E5 and E7, had important effects on the activity of the 1.2 kb sheep myostatin promoter. In addition, we also detected several other important motifs such as MTBF (muscle-specific Mt binding factor), MEF2 (myocyte enhancer factor 2), GRE (glucocorticoid response elements) and PRE (progesterone response elements) along the sheep myostatin promoter by the mutational analysis.

• Journal of Life Science
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• v.5 no.4
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• pp.162-169
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• 1995

The glpD genes encoding gly-3-p dehydrogenase is essential for the aerobic growth of E. coli on glycerol or gly-3-p. The glpE gene, the function of which is unknownm is transcribed divergently with respect to glpD gene. Expression of the adjacent but divergently transcribed glpD the glpE genes is positively regulated by the cAMP-CRP complex. In this study, for a precise investigation of the functional elements in the regulatory region for transcription activation by cAMP-CRP, deletion mutation have been introducted into the regulatory region. The effect of the deletion mutant on transcriptional regulation was tested in vivo by $\beta$-galctosidase activity. Deletion mutants in the regulatory region of glpD demonstrated that the presence of the CRP-binding site resulted in an sixfold increase in promoter activity. And also deletion mutants of glpE gene demonstrated that the presence of the CRP-binding site resulted in an eightfold increase in promoter activity. Insertion of 22 bp oligomer in the deletion mutants has shown that the CRP binding site is need for maximal expression of glpD and glpE genes. glpD and glpE gene, cAMP-CRP complex, deletion mutant, transcriptional regulation.

• BMB Reports
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• v.44 no.3
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• pp.147-157
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• 2011

The meiotic process from the primordial stage to zygote in female germ cells is mainly adjusted by post-transcriptional regulation of pre-existing maternal mRNA and post-translational modification of proteins. Several key proteins such as the cell cycle regulator, Cdk1/cyclin B, are post-translationally modified for precise control of meiotic progression. The second messenger (cAMP), kinases (PKA, Akt, MAPK, Aurora A, CaMK II, etc), phosphatases (Cdc25, Cdc14), and other proteins (G-protein coupled receptor, phosphodiesterase) are directly or indirectly involved in this process. Many proteins, such as CPEB, maskin, eIF4E, eIF4G, 4E-BP, and 4E-T, post-transcriptionally regulate mRNA via binding to the cap structure at the 5' end of mRNA or its 3' untranslated region (UTR) to generate a closed-loop structure. The 3' UTR of the transcript is also implicated in post-transcriptional regulation through an association with proteins such as CPEB, CPSF, GLD-2, PARN, and Dazl to modulate poly(A) tail length. RNA interfering is a new regulatory mechanism of the amount of mRNA in the mouse oocyte. This review summarizes information about post-transcriptional and post-translational regulation during mouse oocyte meiotic maturation.

• Biomolecules & Therapeutics
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• v.29 no.6
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• pp.667-677
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• 2021

The elevated expression of the hyaluronan-mediated motility receptor (HMMR) is known to be highly associated with tumor progression in prostate cancer, but the molecular mechanisms underlying the regulation of HMMR expression remain unclear. Here, we report that mammalian target of rapamycin (mTOR) is a key regulator of HMMR expression, for which its kinase activity is required. Pharmacological inhibitors of mTOR, such as rapamycin and Torin2, markedly suppressed the mRNA level as well as the protein level of HMMR in LNCaP and PC-3 cells. Our data demonstrate that such regulation occurs at the transcription level. HMMR promoter reporter assays revealed that the transcription factor SRF is responsible for the mTOR-mediated transcriptional regulation of HMMR gene. Consistently, the suppression of HMMR expression by Torin2 was noticeably reversed by the overexpression of SRF. Moreover, our findings suggest that the SRF binding sites responsible for the transcriptional regulation of HMMR through the mTOR-SRF axis are located in HMMR promoter sequences carrying the first intron, downstream of the translational start site. Furthermore, the upregulation of HMMR by DHT was abolished by stimulation with rapamycin, prior to DHT treatment, suggesting that mTOR activity is required for the induction of HMMR expression by androgen. Collectively, our study provides new mechanistic insights into the role of mTOR/SRF/AR signaling in HMMR regulation in prostate cancer cells.

• BMB Reports
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• v.42 no.7
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• pp.421-426
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• 2009

Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.