• Title/Summary/Keyword: transcriptional regulator

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Inferring Transcriptional Interactions and Regulator Activities from Experimental Data

  • Wang, Rui-Sheng;Zhang, Xiang-Sun;Chen, Luonan
    • 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.

Interspecies Complementation of the LuxR Family Pathway-Specific Regulator Involved in Macrolide Biosynthesis

  • Mo, SangJoon;Yoon, Yeo Joon
    • Journal of Microbiology and Biotechnology
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    • v.26 no.1
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    • pp.66-71
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    • 2016
  • PikD is a widely known pathway-specific regulator for controlling pikromycin production in Streptomyces venezuelae ATCC 15439, which is a representative of the large ATP-binding regulator of the LuxR family (LAL) in Streptomyces sp. RapH and FkbN also belong to the LAL family of transcriptional regulators, which show greatest homology with the ATP-binding motif and helix-turn-helix DNA-binding motif of PikD. Overexpression of pikD and heterologous expression of rapH and fkbN led to enhanced production of pikromycin by approximately 1.8-, 1.6-, and 1.6-fold in S. venezuelae, respectively. Cross-complementation of rapH and fkbN in the pikD deletion mutant (ΔpikD) restored pikromycin and derived macrolactone production. Overall, these results show that heterologous expression of rapH and fkbN leads to the overproduction of pikromycin and its congeners from the pikromycin biosynthetic pathway in S. venezuelae, and they have the same functionality as the pathwayspecific transcriptional activator for the pikromycin biosynthetic pathway in the ΔpikD strain. These results also show extensive "cross-communication" between pathway-specific regulators of streptomycetes and suggest revision of the current paradigm for pathwayspecific versus global regulation of secondary metabolism in Streptomyces species.

Heterologous Expression of Streptomyces albus Genes Linked to an Integrating Element and Activation of Antibiotic Production

  • Kwon, Hyung-Jin;Lee, Soon-Youl;Hong, Soon-Kwang;Park, Uhn-Mee;Suh, Joo-Won
    • Journal of Microbiology and Biotechnology
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    • v.9 no.4
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    • pp.488-497
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    • 1999
  • Probing Streptomyces albus ATCC 21838 chromosomal DNA with a proline tRNA sequence resulted in an isolation of a putative integrating element in the 6.4-kb EcoRI fragment. It was found that Streptomyces lividans TK-24 transformed with a cloned DNA fragment on a multicopy plasmid, produced a higher level of spore pigment and mycelial red pigment on a regeneration agar. Furthermore, the transformant S. lividans TK-24 produced a markedly increased level of undecylprodigiosin in a broth culture. A nucleotide sequence analysis of the cloned region revealed several open reading frames homologous to the integrases of integrating plasmids or temperate bacteriophages, signal-transducing regulatory proteins with a conserved ATP-binding domain, oxidoreductases ($\beta$-ketoacyl reductase), and an AraC-like transcriptional regulator. To examine the effect on antibiotic production, each coding region was overexpressed separately from the other genes in the region in S. lividans TK-24 with; pJHS3044 for the expression of the signal-transducing regulatory protein homologue, pJHS3045 for the homologue of oxidoreductase, and pJHS3051 for the homologue of the AraC-like transcriptional regulator. Phenotypic studies of S. lividans TK-24 strains harboring plasmids for the overexpression of individual genes suggested the following effects of the genes on antibiotic production: The oxidoreductase homologue stimulated the production of actinorhodin and undecylprodigiosin, which was influenced by the culture conditions; the homologue of the AraC-like transcriptional regulator was the most effective factor in antibiotic production within all the culture conditions tested; the signal-transducing regulatory protein homologue repressed the effect due to the homologue of the AraC-like transcriptional regulator, however, the antibiotic production was derepressed upon entering the stationary phase.

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Subcloning and DNA Sequencing of the Phenol Regulatory Genes in Ralstonia eutropha JMP134 (Ralstonia eutropha JMP134에서 페놀분해에 관여하는 조절유전자의 Subcloning 및 염기서열 분석)

  • ;Subramanian Chitra
    • Korean Journal of Microbiology
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    • v.38 no.4
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    • pp.260-266
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    • 2002
  • In this study, chromosomal DNA fragment related to the regulation of phenol metabolism in Ralstonia eutropha JMP 134 was cloned and sequenced. The result has shown that two open reading frames (ORF1 and ORF2) exist on this regulatory region. ORF1, which initiates from 454 bp downstream of the stop codon of the phenol hydroxylase genes, was found to be composed of 501 amino acids. ORF2, whose start codon is overlapped with the stop codon of ORFl, was found to contain 232 amino acids. The comparison of amino acid sequences with other proteins has revealed that ORF1 belongs to the family of NtrC transcriptional activator, whereas ORF2 shares high homology with the family of GntR protein, which is known to be a negative regulator. ORF1 and ORF2 were designated as a putative positive regulator, phlR2 and a negative regulator phlA, respectively. Possible regulatory mechanisms of phenol metabolism in this strain was discussed.

T-Cell Death-Associated Gene 51 Is a Novel Negative Regulator of PPARγ That Inhibits PPARγ-RXRα Heterodimer Formation in Adipogenesis

  • Kim, Sumi;Lee, Nari;Park, Eui-Soon;Yun, Hyeongseok;Ha, Tae-Uk;Jeon, Hyoeun;Yu, Jiyeon;Choi, Seunga;Shin, Bongjin;Yu, Jungeun;Rhee, Sang Dal;Choi, Yongwon;Rho, Jaerang
    • Molecules and Cells
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    • v.44 no.1
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    • pp.1-12
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    • 2021
  • The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the master transcriptional regulator in adipogenesis. PPARγ forms a heterodimer with another nuclear receptor, retinoid X receptor (RXR), to form an active transcriptional complex, and their transcriptional activity is tightly regulated by the association with either coactivators or corepressors. In this study, we identified T-cell death-associated gene 51 (TDAG51) as a novel corepressor of PPARγ-mediated transcriptional regulation. We showed that TDAG51 expression is abundantly maintained in the early stage of adipogenic differentiation. Forced expression of TDAG51 inhibited adipocyte differentiation in 3T3-L1 cells. We found that TDAG51 physically interacts with PPARγ in a ligand-independent manner. In deletion mutant analyses, large portions of the TDAG51 domains, including the pleckstrin homology-like, glutamine repeat and proline-glutamine repeat domains but not the proline-histidine repeat domain, are involved in the interaction with the region between residues 140 and 506, including the DNA binding domain, hinge, ligand binding domain and activation function-2 domain, in PPARγ. The heterodimer formation of PPARγ-RXRα was competitively inhibited in a ligand-independent manner by TDAG51 binding to PPARγ. Thus, our data suggest that TDAG51, which could determine adipogenic cell fate, acts as a novel negative regulator of PPARγ by blocking RXRα recruitment to the PPARγ-RXRα heterodimer complex in adipogenesis.

BolA Affects Cell Growth, and Binds to the Promoters of Penicillin-Binding Proteins 5 and 6 and Regulates Their Expression

  • Guinote, Ines Batista;Matos, Rute Goncalves;Freire, Patrick;Arraiano, Cecilia Maria
    • Journal of Microbiology and Biotechnology
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    • v.21 no.3
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    • pp.243-251
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    • 2011
  • The gene bolA was discovered in the 80's, but unraveling its function in the cell has proven to be a complex task. The BolA protein has pleiotropic effects over cell physiology, altering growth and morphology, inducing biofilm formation, and regulating the balance of several membrane proteins. Recently, BolA was shown to be a transcription factor by repressing the expression of the mreB gene. The present report shows that BolA is a transcriptional regulator of the dacA and dacC genes, thus regulating both DD-carboxypeptidases PBP5 and PBP6 and thereby demonstrating the versatility of BolA as a cellular regulator. In this work, we also demonstrate that reduction of cell growth and survival can be connected to the overexpression of the bolA gene in different E. coli backgrounds, particularly in the exponential growth phase. The most interesting finding is that overproduction of BolA affects bacterial growth differently depending on whether the cells were inoculated directly from a plate culture or from an overnight batch culture. This strengthens the idea that BolA can be engaged in the coordination of genes that adapt the cell physiology in order to enhance cell adaptation and survival under stress conditions.

GzRUM1, Encoding an Ortholog of Human Retinoblastoma Binding Protein 2, is Required for Ascospore Development in Gibberella zeae

  • Kim, Hee-Kyoung;Lee, Yin-Won;Yun, Sung-Hwan
    • The Plant Pathology Journal
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    • v.27 no.1
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    • pp.20-25
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    • 2011
  • Gibberella zeae (anamorph: Fusarium graminearum), a homothallic (self-ferile) ascomycete with ubiquitous geographic distribution, causes serious diseases in several cereal crops. Ascospores (sexual spores) produced by this fungal pathogen have been suggested as the main source of primary inoculum in disease development. Here, we report the function of a gene designated GzRUM1, which is essential for ascospore formation in G. zeae. The deduced product of GzRUM1 showed significant similarities to the human retinoblastoma (tumor suppressor) binding protein 2 and a transcriptional repressor, Rum1 in the corn smut fungus (Ustilago maydis). The transcript of GzRUM1 was detected during the both vegetative and sexual stages, but was more highly accumulated during the latter stage. In addition, no GzRUM1 transcript was detected in a G. zeae strain lacking a mating-type gene (MAT1-2), a master regulator for sexual development in G. zeae. Targeted deletion of GzRUM1 caused no dramatic changes in several traits except ascospore formation. The ${\Delta}$GzRUM1 strain produced perithecia (sexual fruit bodies) but not asci nor ascospores within them. This specific defect leading to an arrest in ascospore development suggests that GzRUM1, as Rum1 in U. maydis, functions as a transcriptional regulator during sexual reproduction in G. zeae.