• Title/Summary/Keyword: genetic regulation

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Genetic Regulation of Corynebacterium glutamicum Metabolism

  • Wendisch Volker F.
    • Journal of Microbiology and Biotechnology
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    • v.16 no.7
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    • pp.999-1009
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    • 2006
  • Physiological, biochemical and genetic studies of Corynebacterium glutamicum, a workhorse of white biotechnology used for amino acid production, led to a waste knowledge mainly about amino acid biosynthetic pathways and the central carbon metabolism of this bacterium. Spurred by the availability of the genome sequence and of genome-based experimental methods such as DNA microarray analysis, research on genetic regulation came into focus. Recent progress on mechanisms of genetic regulation of the carbon, nitrogen, sulfur and phosphorus metabolism in C. glutamicum will be discussed.

State-Space Approach to Modeling Dynamics of Gene Regulation in Networks

  • Xiong, Momiao;Jin, Li
    • Proceedings of the Korean Society for Bioinformatics Conference
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    • 2005.09a
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    • pp.191-196
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    • 2005
  • Genetic networks are a key to unraveling dynamic properties of biological processes and regulation of genes plays an essential role in dynamic behavior of the genetic networks. A popular characterization of regulation of the gene is a kinetic model. However, many kinetic parameters in the genetic regulation have not been available. To overcome this difficulty, in this report, state-space approach to modeling gene regulation is presented. Second-order systems are used to characterize gene regulation. Interpretation of coefficients in the second order systems as resistance, capacitance and inductance is studied. The mathematical methods for transient response analysis of gene regulation to external perturbation are investigated. Criterion for classifying gene into three categories: underdamped, overdamped and critical damped is discussed. The proposed models are applied to yeast cell cycle gene expression data.

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Caffeine inhibits adipogenesis through modulation of mitotic clonal expansion and the AKT/GSK3 pathway in 3T3-L1 adipocytes

  • Kim, Hyo Jung;Yoon, Bo Kyung;Park, Hyounkyoung;Seok, Jo Woon;Choi, Hyeonjin;Yu, Jung Hwan;Choi, Yoonjeong;Song, Su Jin;Kim, Ara;Kim, Jae-woo
    • BMB Reports
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    • v.49 no.2
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    • pp.111-115
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    • 2016
  • Caffeine has been proposed to have several beneficial effects on obesity and its related metabolic diseases; however, how caffeine affects adipocyte differentiation has not been elucidated. In this study, we demonstrated that caffeine suppressed 3T3-L1 adipocyte differentiation and inhibited the expression of CCAAT/enhancer binding protein (C/EBP)α and peroxisome proliferator-activated receptor (PPAR)γ, two main adipogenic transcription factors. Anti-adipogenic markers, such as preadipocyte secreted factor (Pref)-1 and Krüppel-like factor 2, remained to be expressed in the presence of caffeine. Furthermore, 3T3-L1 cells failed to undergo typical mitotic clonal expansion in the presence of caffeine. Investigation of hormonal signaling revealed that caffeine inhibited the activation of AKT and glycogen synthase kinase (GSK) 3 in a dose-dependent manner, but not extracellular signal-regulated kinase (ERK). Our data show that caffeine is an anti-adipogenic bioactive compound involved in the modulation of mitotic clonal expansion during adipocyte differentiation through the AKT/GSK3 pathway.

Genetic Architecture of Transcription and Chromatin Regulation

  • Kim, Kwoneel;Bang, Hyoeun;Lee, Kibaick;Choi, Jung Kyoon
    • Genomics & Informatics
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    • v.13 no.2
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    • pp.40-44
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    • 2015
  • DNA microarray and next-generation sequencing provide data that can be used for the genetic analysis of multiple quantitative traits such as gene expression levels, transcription factor binding profiles, and epigenetic signatures. In particular, chromatin opening is tightly coupled with gene transcription. To understand how these two processes are genetically regulated and associated with each other, we examined the changes of chromatin accessibility and gene expression in response to genetic variation by means of quantitative trait loci mapping. Regulatory patterns commonly observed in yeast and human across different technical platforms and experimental designs suggest a higher genetic complexity of transcription regulation in contrast to a more robust genetic architecture of chromatin regulation.

Reconstructed Adeno-Associated Virus with the Extracellular Domain of Murine PD-1 Induces Antitumor Immunity

  • Elhag, Osama A.O.;Hu, Xiao-Jing;Wen-Ying, Zhang;Li, Xiong;Yuan, Yong-Ze;Deng, Ling-Feng;Liu, De-Li;Liu, Ying-Le;Hui, Geng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.4031-4036
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    • 2012
  • Background: The negative signaling provided by interactions of the co-inhibitory molecule, programmed death-1 (PD-1), and its ligands, B7-H1 (PD-L1) and B7-DC (PD-L2), is a critical mechanism contributing to tumor evasion; blockade of this pathway has been proven to enhance cytotoxic activity and mediate antitumor therapy. Here we evaluated the anti-tumor efficacy of AAV-mediated delivery of the extracellular domain of murine PD-1 (sPD-1) to a tumor site. Material and Methods: An rAAV vector was constructed in which the expression of sPD-1, a known negative regulator of TCR signals, is driven by human cytomegalovirus immediate early promoter (CMV-P), using a triple plasmid transfection system. Tumor-bearing mice were then treated with the AAV/sPD1 construct and expression of sPD-1 in tumor tissues was determined by semi quantitative RT-PCR, and tumor weights and cytotoxic activity of splenocytes were measured. Results: Analysis of tumor homogenates revealed sPD-1 mRNA to be significantly overexpressed in rAAV/sPD-1 treated mice as compared with control levels. Its use for local gene therapy at the inoculation site of H22 hepatoma cells could inhibit tumor growth, also enhancing lysis of tumor cells by lymphocytes stimulated specifically with an antigen. In addition, PD-1 was also found expressed on the surfaces of activated CD8+ T cells. Conclusion: This study confirmed that expression of the soluble extracellular domain of PD-1 molecule could reduce tumor microenvironment inhibitory effects on T cells and enhance cytotoxicity. This suggests that it might be a potential target for development of therapies to augment T-cell responses in patients with malignancies.

A Discrete Mathematical Model Applied to Genetic Regulation and Metabolic Networks

  • Asenjo, J.A.;Ramirez, P.;Rapaport, I.;Aracena, J.;Goles, E.;Andrews, B.A.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.3
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    • pp.496-510
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    • 2007
  • This paper describes the use of a discrete mathematical model to represent the basic mechanisms of regulation of the bacteria E. coli in batch fermentation. The specific phenomena studied were the changes in metabolism and genetic regulation when the bacteria use three different carbon substrates (glucose, glycerol, and acetate). The model correctly predicts the behavior of E. coli vis-a-vis substrate mixtures. In a mixture of glucose, glycerol, and acetate, it prefers glucose, then glycerol, and finally acetate. The model included 67 nodes; 28 were genes, 20 enzymes, and 19 regulators/biochemical compounds. The model represents both the genetic regulation and metabolic networks in an integrated form, which is how they function biologically. This is one of the first attempts to include both of these networks in one model. Previously, discrete mathematical models were used only to describe genetic regulation networks. The study of the network dynamics generated 8 $(2^3)$ fixed points, one for each nutrient configuration (substrate mixture) in the medium. The fixed points of the discrete model reflect the phenotypes described. Gene expression and the patterns of the metabolic fluxes generated are described accurately. The activation of the gene regulation network depends basically on the presence of glucose and glycerol. The model predicts the behavior when mixed carbon sources are utilized as well as when there is no carbon source present. Fictitious jokers (Joker1, Joker2, and Repressor SdhC) had to be created to control 12 genes whose regulation mechanism is unknown, since glycerol and glucose do not act directly on the genes. The approach presented in this paper is particularly useful to investigate potential unknown gene regulation mechanisms; such a novel approach can also be used to describe other gene regulation situations such as the comparison between non-recombinant and recombinant yeast strain, producing recombinant proteins, presently under investigation in our group.

HOTAIR Long Non-coding RNA: Characterizing the Locus Features by the In Silico Approaches

  • Hajjari, Mohammadreza;Rahnama, Saghar
    • Genomics & Informatics
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    • v.15 no.4
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    • pp.170-177
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    • 2017
  • HOTAIR is an lncRNA that has been known to have an oncogenic role in different cancers. There is limited knowledge of genetic and epigenetic elements and their interactions for the gene encoding HOTAIR. Therefore, understanding the molecular mechanism and its regulation remains to be challenging. We used different in silico analyses to find genetic and epigenetic elements of HOTAIR gene to gain insight into its regulation. We reported different regulatory elements including canonical promoters, transcription start sites, CpGIs as well as epigenetic marks that are potentially involved in the regulation of HOTAIR gene expression. We identified repeat sequences and single nucleotide polymorphisms that are located within or next to the CpGIs of HOTAIR. Our analyses may help to find potential interactions between genetic and epigenetic elements of HOTAIR gene in the human tissues and show opportunities and limitations for researches on HOTAIR gene in future studies.

Regulation of Ferritin Synthesis by Iron-responsive Element in 5'-Untranslated Region (5'-Untranslated Region에 존재하는 Iron Responsive Element에 의한 Ferritin 합성조절)

  • Chung, In-Sik;Lee, Jung-Lim;Kim, Hae-Yeong
    • Applied Biological Chemistry
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    • v.41 no.3
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    • pp.224-227
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    • 1998
  • The expression of ferritin involved in iron metabolism is regulated at the translational level by the interaction of iron regulatory protein with iron-responsive element(IRE) in the 5'-untranslated region of ferritin transcript. To identify the role of structural element utilized for translational regulation of ferritin, we studied the effects of mutations in the ferritin IRE by measuring IRP binding activity and translational activity. Our data suggest that the cytosine at bulged position of IRE within ferritin is important for the formation of RNA secondary structure involved in translational regulation.

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