• Title/Summary/Keyword: Gene Regulation

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Prediction of functional molecular machanism of Astragalus membranaceus on obesity via network pharmacology analysis (네트워크 약리학을 통한 황기의 항비만 효능 및 작용기전 예측 연구)

  • Mi Hye, Kim
    • The Korea Journal of Herbology
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    • v.38 no.1
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    • pp.45-53
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    • 2023
  • Objectives : Network pharmacology-based research is one of useful tool to predict the possible efficacy and molecular mechanisms of natural materials with multi compounds-multi targeting effects. In this study, we investigated the functional underlying mechanisms of Astragalus membranaceus Bunge (AM) on its anti-obesity effects using a network pharmacology analysis. Methods : The constituents of AM were collected from public databases and its target genes were gathered from PubChem database. The target genes of AM were compared with the gene set of obesity to find the correlation. Then, the network was constructed by Cytoscape 3.9.1. and functional enrichment analysis was conducted to predict the most relevant pathway of AM. Results : The result showed that AM network contained the 707 nodes and 6867 edges, and 525 intersecting genes were exhibited between AM and obesity gene set, indicating that high correlation with the effects of AM on obesity. Based on GO biological process and KEGG Pathway, 'Response to lipid', 'Cellular response to lipid', 'Lipid metabolic process', 'Regulation of chemokine production', 'Regulation of lipase activity', 'Chemokine signaling pathway', 'Regulation of lipolysis in adipocytes' and 'PPAR signaling pathway' were predicted as functional pathways of AM on obesity. Conclusions : AM showed high relevance with the lipid metabolism related with the chemokine production and lipolysis pathways. This study could be a basis that AM has promising effects on obesity via network pharmacology analysis.

Growth retardation and differential regulation of expansin genes in chilling-stressed sweetpotato

  • Noh, Seol Ah;Park, Sun Hee;Huh, Gyung Hye;Paek, Kyung-Hee;Shin, Jeong Sheop;Bae, Jung Myung
    • Plant Biotechnology Reports
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    • v.3 no.1
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    • pp.75-85
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    • 2009
  • We report here a first evaluation of chilling-responsive gene regulation in the sweetpotato. The growth of sweetpotato plants was severely retarded at $12^{\circ}C$; the lengths of the leaf, petiole, and root were markedly reduced and microscopic observation revealed that the elongation growth of the epidermal cells in each of these organs was significantly reduced. We examined the transcriptional regulation of three sweetpotato expansin genes (IbEXP1, IbEXP2 and IbEXPL1) in response to various chilling temperatures (12, 16, 22, and $28^{\circ}C$). In the leaf and petiole, the highest transcript levels were those of IbEXP1 at $28^{\circ}C$, whereas IbEXPL1 transcript levels were highest in the root. IbEXP1 mRNA levels in the $12^{\circ}C-treated$ petiole showed a fluctuating pattern (transient decrease-recovery-stable decrease) for 48 h. In the leaf and petiole, IbEXP1 and IbEXPL1 exhibited a similar response to chilling in that their mRNA levels decreased at $22^{\circ}C$, increased at $16^{\circ}C$, and decreased dramatically at $12^{\circ}C$. In contrast, mRNA levels of IbEXP2 in the leaf fell gradually as the temperature fell from 28 to $12^{\circ}C$, while they remained unaltered in the petiole. In the root, mRNA levels of IbEXPL1 and IbEXP1 reached maximum levels at $16^{\circ}C$, and decreased significantly at $12^{\circ}C$. These data demonstrated that expression of these three expansin genes was ultimately down-regulated at $12^{\circ}C$; however, transcriptional regulation of each expansin gene exhibited its own distinctive pattern in response to various chilling temperatures.

cAMP/PKA Agonist Restores the Fasting-Induced Down-Regulation of nNOS Expression in the Paraventricular Nucleus

  • Yoo, Sang-Bae;Lee, Seoul;Lee, Joo-Young;Kim, Bom-Taeck;Lee, Jong-Ho;Jahng, Jeong-Won
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.5
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    • pp.333-337
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    • 2012
  • Gene expression of neuronal nitric oxide synthase (nNOS) changes in the hypothalamic paraventricular nucleus (PVN) depending on feeding conditions, which is decreased during food deprivation and restored by refeeding, and phosphorylated cAMP response element binding protein (pCREB) was suggested to play a role in its regulation. This study was conducted to examine if the fasting-induced down-regulation of the PVN-nNOS expression is restored by activation of cAMP-dependent protein kinase A (cAMP/PKA) pathway. Freely moving rats received intracerebroventricular (icv) injection of cAMP/PKA activator Sp-cAMP (40 nmol) or vehicle (sterilized saline) following 48 h of food deprivation. One hour after drug injections, rats were transcardially perfused with 4% paraformaldehyde, and the PVN tissues were processed for nNOS or pCREB immunohistochemistry. Sp-cAMP significantly increased not only nNOS but also pCREB immunoreactivities in the PVN of food deprived rats. Fastinginduced down-regulation of the PVN-nNOS was restored by 1 h after the icv Sp-cAMP. Results suggest that cAMP/PKA pathway may mediate the regulation of the PVN-nNOS expression depending on different feeding conditions.

Inhibition of the Interleukin-11-STAT3 Axis Attenuates Hypoxia-Induced Migration and Invasion in MDA-MB-231 Breast Cancer Cells

  • Lim, Ji-Hong
    • The Korean Journal of Physiology and Pharmacology
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    • v.18 no.5
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    • pp.391-396
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    • 2014
  • Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone

  • Lim, Ji-Ae;Kim, Sang-Hoon
    • 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.

Histone H4-Specific Deacetylation at Active Coding Regions by Hda1C

  • Lee, Min Kyung;Kim, TaeSoo
    • Molecules and Cells
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    • v.43 no.10
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    • pp.841-847
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    • 2020
  • Histone acetylation and deacetylation play central roles in the regulation of chromatin structure and transcription by RNA polymerase II (RNA Pol II). Although Hda1 histone deacetylase complex (Hda1C) is known to selectively deacetylate histone H3 and H2B to repress transcription, previous studies have suggested its potential roles in histone H4 deacetylation. Recently, we have shown that Hda1C has two distinct functions in histone deacetylation and transcription. Histone H4-specific deacetylation at highly transcribed genes negatively regulates RNA Pol II elongation and H3 deacetylation at inactive genes fine-tunes the kinetics of gene induction upon environmental changes. Here, we review the recent understandings of transcriptional regulation via histone deacetylation by Hda1C. In addition, we discuss the potential mechanisms for histone substrate switching by Hda1C, depending on transcriptional frequency and activity.

Use of .lambda.gt 11 and antibody probes to isolate genes encoding RNA polymerase subunits from bacillus subtilis

  • Suh, Joo-Won;Price, Chester
    • The Microorganisms and Industry
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    • v.14 no.1
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    • pp.17-20
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    • 1988
  • A genetic analysis of the complex Bacillus subtilis transcriptional apparatus is essential to understand the function, regulation, and interaction of the transcriptase components during growth and sporulation. This approach in Escherichia coli has uncovered fundamental mechanisms regulating gene expression Cole and Nomura, 1986; Lindahl and Zengel, 1986) and an analysis of the B. subtilis transcriptase will allow comoparison of the E.coli system to another bacterium that has evolved under different selective pressures. To this end we used antibody probes to isolate the alpha, beta, and beta' core subunit genes from a .lambda.gtill expression vector library. To address the question of function ans regulation of the minor sigma factors that confer promoter specifity on the polymerase core (Losick et al., 1986), we used the same approach to isolate the gene for the 37,000 dalton sigma factor, sigma-37.

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RNA-Protein Interactions and Protein-Protein Interactions during Regulation of Eukaryotic Gene Expression

  • Varani, Luca;Ramos, Andres;Cole, Pual T.;Neuhaus, David;Varani, Gabriele
    • Journal of the Korean Magnetic Resonance Society
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    • v.2 no.2
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    • pp.152-157
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    • 1998
  • The diversity of RNA functions ranges from storage and propagation of genetic information to enzymatic activity during RNA processing and protein synthesis. This diversity of functions requires an equally diverse arrays of structures, and, very often, the formation of functional RNA-protein complexes. Recognition of specific RNA signals by RNA-binding proteins is central to all aspects of post-transcriptional regulation of gene expression. We will describe how NMR is being used to understand at the atomic level how these important biological processes occur.

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The diverse roles of RNA polymerase II C-terminal domain phosphatase SCP1

  • Harikrishna, Reddy R.;Kim, Hackyoung;Noh, Kwangmo;Kim, Young Jun
    • BMB Reports
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    • v.47 no.4
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    • pp.192-196
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    • 2014
  • RNA polymerase II carboxyl-terminal domain (pol II CTD) phosphatases are a newly emerging family of phosphatases that are members of DXDX (T/V). The subfamily includes Small CTD phosphatases, like SCP1, SCP2, SCP3, TIMM50, HSPC129 and UBLCP. Extensive study of SCP1 has elicited the diversified roles of the small C terminal domain phosphatase. The SCP1 plays a vital role in various biological activities, like neuronal gene silencing and preferential Ser5 dephosphorylation, acts as a cardiac hypertrophy inducer with the help of its intronic miRNAs, and has shown a key role in cell cycle regulation. This short review offers an explanation of the mechanism of action of small CTD phosphatases, in different biological activities and metabolic processes.

Machine Learning Applied to Uncovering Gene Regulation

  • Craven, Mark
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2000.11a
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    • pp.61-68
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    • 2000
  • Now that the complete genomes of numerous organisms have been ascertained, key problems in molecular biology include determining the functions of the genes in each organism, the relationships that exist among these genes, and the regulatory mechanisms that control their operation. These problems can be partially addressed by using machine learning methods to induce predictive models from available data. My group is applying and developing machine learning methods for several tasks that involve characterizing gene regulation. In one project, for example, we are using machine learning methods to identify transcriptional control elements such as promoters, terminators and operons. In another project, we are using learning methods to identify and characterize sets of genes that are affected by tumor promoters in mammals. Our approach to these tasks involves learning multiple models for inter-related tasks, and applying learning algorithms to rich and diverse data sources including sequence data, microarray data, and text from the scientific literature.

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