Artykuły w czasopismach: „Regulatory genes”

1

Li, Ling, i Harald Vaessin. "Pan-neural Prospero terminates cell proliferation during Drosophila neurogenesis". Genes & Development 14, nr 2 (15.01.2000): 147–51. http://dx.doi.org/10.1101/gad.14.2.147.

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Organogenesis requires coordination between developmental specific regulators and genes governing cell proliferation. Here we show thatDrosophila prospero encodes a critical regulator of the transition from mitotically active cells to terminal differentiated neurons. Loss of pros results in aberrant expression of multiple cell-cycle regulatory genes and ectopic mitotic activity. In contrast, ectopic pros expression causes transcriptional suppression of multiple cell-cycle regulatory genes and premature termination of cell division. pros activity, hence, provides a critical regulatory link between neuronal lineage development and transcriptional regulation of cell cycle regulatory genes.

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Piro, Rosario Michael. "Are all genes regulatory genes?" Biology & Philosophy 26, nr 4 (29.03.2011): 595–602. http://dx.doi.org/10.1007/s10539-011-9251-9.

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Green, A. R., i J. A. Wyke. "NEGATIVE REGULATORY GENES". Lancet 326, nr 8469-8470 (grudzień 1985): 1434. http://dx.doi.org/10.1016/s0140-6736(85)92607-8.

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Chaturongakul, Soraya, Sarita Raengpradub, M. Elizabeth Palmer, Teresa M. Bergholz, Renato H. Orsi, Yuewei Hu, Juliane Ollinger, Martin Wiedmann i Kathryn J. Boor. "Transcriptomic and Phenotypic Analyses Identify Coregulated, Overlapping Regulons among PrfA, CtsR, HrcA, and the Alternative Sigma Factors σB, σC, σH, and σLinListeria monocytogenes". Applied and Environmental Microbiology 77, nr 1 (29.10.2010): 187–200. http://dx.doi.org/10.1128/aem.00952-10.

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ABSTRACTA set of sevenListeria monocytogenes10403S mutant strains, each bearing an in-frame null mutation in a gene encoding a key regulatory protein, was used to characterize transcriptional networks inL. monocytogenes; the seven regulatory proteins addressed include all fourL. monocytogenesalternative sigma factors (σB, σC, σH, and σL), the virulence gene regulator PrfA, and the heat shock-related negative regulators CtsR and HrcA. Whole-genome microarray analyses, used to identify regulons for each of these 7 transcriptional regulators, showed considerable overlap among regulons. Among 188 genes controlled by more than one regulator, 176 were coregulated by σB, including 92 genes regulated by both σBand σH(with 18 of these genes coregulated by σB, σH, and at least one additional regulator) and 31 genes regulated by both σBand σL(with 10 of these genes coregulated by σB, σL, and at least one additional regulator). Comparative phenotypic characterization measuring acid resistance, heat resistance, intracellular growth in J774 cells, invasion into Caco-2 epithelial cells, and virulence in the guinea pig model indicated contributions of (i) σBto acid resistance, (ii) CtsR to heat resistance, and (iii) PrfA, σB, and CtsR to virulence-associated characteristics. Loss of the remaining transcriptional regulators (i.e.,sigH,sigL, orsigC) resulted in limited phenotypic consequences associated with stress survival and virulence. Identification of overlaps among the regulons provides strong evidence supporting the existence of complex regulatory networks that appear to provide the cell with regulatory redundancies, along with the ability to fine-tune gene expression in response to rapidly changing environmental conditions.

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Mern, Demissew S., Seung-Wook Ha, Viola Khodaverdi, Nicole Gliese i Helmut Görisch. "A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators". Microbiology 156, nr 5 (1.05.2010): 1505–16. http://dx.doi.org/10.1099/mic.0.032847-0.

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In addition to the known response regulator ErbR (former AgmR) and the two-component regulatory system EraSR (former ExaDE), three additional regulatory proteins have been identified as being involved in controlling transcription of the aerobic ethanol oxidation system in Pseudomonas aeruginosa. Two putative sensor kinases, ErcS and ErcS′, and a response regulator, ErdR, were found, all of which show significant similarity to the two-component flhSR system that controls methanol and formaldehyde metabolism in Paracoccus denitrificans. All three identified response regulators, EraR (formerly ExaE), ErbR (formerly AgmR) and ErdR, are members of the luxR family. The three sensor kinases EraS (formerly ExaD), ErcS and ErcS′ do not contain a membrane domain. Apparently, they are localized in the cytoplasm and recognize cytoplasmic signals. Inactivation of gene ercS caused an extended lag phase on ethanol. Inactivation of both genes, ercS and ercS′, resulted in no growth at all on ethanol, as did inactivation of erdR. Of the three sensor kinases and three response regulators identified thus far, only the EraSR (formerly ExaDE) system forms a corresponding kinase/regulator pair. Using reporter gene constructs of all identified regulatory genes in different mutants allowed the hierarchy of a hypothetical complex regulatory network to be established. Probably, two additional sensor kinases and two additional response regulators, which are hidden among the numerous regulatory genes annotated in the genome of P. aeruginosa, remain to be identified.

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Koppenhöfer, Sonja, i Andrew S. Lang. "Interactions among Redox Regulators and the CtrA Phosphorelay in Dinoroseobacter shibae and Rhodobacter capsulatus". Microorganisms 8, nr 4 (14.04.2020): 562. http://dx.doi.org/10.3390/microorganisms8040562.

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Bacteria employ regulatory networks to detect environmental signals and respond appropriately, often by adjusting gene expression. Some regulatory networks influence many genes, and many genes are affected by multiple regulatory networks. Here, we investigate the extent to which regulatory systems controlling aerobic–anaerobic energetics overlap with the CtrA phosphorelay, an important system that controls a variety of behavioral processes, in two metabolically versatile alphaproteobacteria, Dinoroseobacter shibae and Rhodobacter capsulatus. We analyzed ten available transcriptomic datasets from relevant regulator deletion strains and environmental changes. We found that in D. shibae, the CtrA phosphorelay represses three of the four aerobic–anaerobic Crp/Fnr superfamily regulator-encoding genes (fnrL, dnrD, and especially dnrF). At the same time, all four Crp/Fnr regulators repress all three phosphorelay genes. Loss of dnrD or dnrF resulted in activation of the entire examined CtrA regulon, regardless of oxygen tension. In R. capsulatus FnrL, in silico and ChIP-seq data also suggested regulation of the CtrA regulon, but it was only with loss of the redox regulator RegA where an actual transcriptional effect on the CtrA regulon was observed. For the first time, we show that there are complex interactions between redox regulators and the CtrA phosphorelays in these bacteria and we present several models for how these interactions might occur.

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Thompson, Catriona M. A., James P. J. Hall, Govind Chandra, Carlo Martins, Gerhard Saalbach, Supakan Panturat, Susannah M. Bird i in. "Plasmids manipulate bacterial behaviour through translational regulatory crosstalk". PLOS Biology 21, nr 2 (14.02.2023): e3001988. http://dx.doi.org/10.1371/journal.pbio.3001988.

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Beyond their role in horizontal gene transfer, conjugative plasmids commonly encode homologues of bacterial regulators. Known plasmid regulator homologues have highly targeted effects upon the transcription of specific bacterial traits. Here, we characterise a plasmid translational regulator, RsmQ, capable of taking global regulatory control in Pseudomonas fluorescens and causing a behavioural switch from motile to sessile lifestyle. RsmQ acts as a global regulator, controlling the host proteome through direct interaction with host mRNAs and interference with the host’s translational regulatory network. This mRNA interference leads to large-scale proteomic changes in metabolic genes, key regulators, and genes involved in chemotaxis, thus controlling bacterial metabolism and motility. Moreover, comparative analyses found RsmQ to be encoded on a large number of divergent plasmids isolated from multiple bacterial host taxa, suggesting the widespread importance of RsmQ for manipulating bacterial behaviour across clinical, environmental, and agricultural niches. RsmQ is a widespread plasmid global translational regulator primarily evolved for host chromosomal control to manipulate bacterial behaviour and lifestyle.

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Gluecksohn-Waelsch, Salome. "Regulatory genes in development". Trends in Genetics 3 (styczeń 1987): 123–27. http://dx.doi.org/10.1016/0168-9525(87)90201-0.

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Lu, Renfei, Hao Tang, Yue Qiu, Wenhui Yang, Huiying Yang, Dongsheng Zhou, Xinxiang Huang, Lingfei Hu i Yiquan Zhang. "Quorum sensing regulates the transcription of lateral flagellar genes in Vibrio parahaemolyticus". Future Microbiology 14, nr 12 (sierpień 2019): 1043–53. http://dx.doi.org/10.2217/fmb-2019-0048.

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Aim: Investigation of the lateral flagellar (Laf) genes transcription by the quorum sensing (QS) regulators AphA and OpaR in Vibrio parahaemolyticus. Materials & methods: Regulation mechanisms were assessed by combined utilization of swarming motility assay, qPCR, LacZ fusion, EMSA and DNase I footprinting. Results: AphA and OpaR oppositely regulate swarming motility and Laf genes. At high cell density, OpaR bound to the regulatory regions of motY-lafK-fliEFGHIJ, fliMNPQR-flhBA, fliDSTKLA-motAB and lafA to repress their transcription. At low cell density, AphA indirectly activated their transcription. Conclusion: OpaR repression of swarming motility was via its direct repression of Laf genes, while AphA exerted its regulatory effect on swarming motility through unknown regulator(s).

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Choi, Jeongjoon, i Eduardo A. Groisman. "Horizontally acquired regulatory gene activates ancestral regulatory system to promote Salmonella virulence". Nucleic Acids Research 48, nr 19 (12.10.2020): 10832–47. http://dx.doi.org/10.1093/nar/gkaa813.

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Abstract Horizontally acquired genes are typically regulated by ancestral regulators. This regulation enables expression of horizontally acquired genes to be coordinated with that of preexisting genes. Here, we report a singular example of the opposite regulation: a horizontally acquired gene that controls an ancestral regulator, thereby promoting bacterial virulence. We establish that the horizontally acquired regulatory gene ssrB is necessary to activate the ancestral regulatory system PhoP/PhoQ of Salmonella enterica serovar Typhimurium (S. Typhimurium) in mildly acidic pH, which S. Typhimurium experiences inside macrophages. SsrB promotes phoP transcription by binding upstream of the phoP promoter. SsrB also increases ugtL transcription by binding to the ugtL promoter region, where it overcomes gene silencing by the heat-stable nucleoid structuring protein H-NS, enhancing virulence. The largely non-pathogenic species S. bongori failed to activate PhoP/PhoQ in mildly acidic pH because it lacks both the ssrB gene and the SsrB binding site in the target promoter. Low Mg2+ activated PhoP/PhoQ in both S. bongori and ssrB-lacking S. Typhimurium, indicating that the SsrB requirement for PhoP/PhoQ activation is signal-dependent. By controlling the ancestral genome, horizontally acquired genes are responsible for more crucial abilities, including virulence, than currently thought.

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Moon, Heungyun, Kap-Hoon Han i Jae-Hyuk Yu. "Upstream Regulation of Development and Secondary Metabolism in Aspergillus Species". Cells 12, nr 1 (20.12.2022): 2. http://dx.doi.org/10.3390/cells12010002.

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In filamentous fungal Aspergillus species, growth, development, and secondary metabolism are genetically programmed biological processes, which require precise coordination of diverse signaling elements, transcription factors (TFs), upstream and downstream regulators, and biosynthetic genes. For the last few decades, regulatory roles of these controllers in asexual/sexual development and primary/secondary metabolism of Aspergillus species have been extensively studied. Among a wide spectrum of regulators, a handful of global regulators govern upstream regulation of development and metabolism by directly and/or indirectly affecting the expression of various genes including TFs. In this review, with the model fungus Aspergillus nidulans as the central figure, we summarize the most well-studied main upstream regulators and their regulatory roles. Specifically, we present key functions of heterotrimeric G proteins and G protein-coupled receptors in signal transduction), the velvet family proteins governing development and metabolism, LaeA as a global regulator of secondary metabolism, and NsdD, a key GATA-type TF, affecting development and secondary metabolism and provide a snapshot of overall upstream regulatory processes underlying growth, development, and metabolism in Aspergillus fungi.

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Adhikari, Satish, Ivan Erill i Patrick D. Curtis. "Transcriptional rewiring of the GcrA/CcrM bacterial epigenetic regulatory system in closely related bacteria". PLOS Genetics 17, nr 3 (11.03.2021): e1009433. http://dx.doi.org/10.1371/journal.pgen.1009433.

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Transcriptional rewiring is the regulation of different target genes by orthologous regulators in different organisms. While this phenomenon has been observed, it has not been extensively studied, particularly in core regulatory systems. Several global cell cycle regulators are conserved in the Alphaproteobacteria, providing an excellent model to study this phenomenon. First characterized in Caulobacter crescentus, GcrA and CcrM compose a DNA methylation-based regulatory system that helps coordinate the complex life cycle of this organism. These regulators are well-conserved across Alphaproteobacteria, but the extent to which their regulatory targets are conserved is not known. In this study, the regulatory targets of GcrA and CcrM were analyzed by SMRT-seq, RNA-seq, and ChIP-seq technologies in the Alphaproteobacterium Brevundimonas subvibrioides, and then compared to those of its close relative C. crescentus that inhabits the same environment. Although the regulators themselves are highly conserved, the genes they regulate are vastly different. GcrA directly regulates 204 genes in C. crescentus, and though B. subvibrioides has orthologs to 147 of those genes, only 48 genes retained GcrA binding in their promoter regions. Additionally, only 12 of those 48 genes demonstrated significant transcriptional change in a gcrA mutant, suggesting extensive transcriptional rewiring between these organisms. Similarly, out of hundreds of genes CcrM regulates in each of these organisms, only 2 genes were found in common. When multiple Alphaproteobacterial genomes were analyzed bioinformatically for potential GcrA regulatory targets, the regulation of genes involved in DNA replication and cell division was well conserved across the Caulobacterales but not outside this order. This work suggests that significant transcriptional rewiring can occur in cell cycle regulatory systems even over short evolutionary distances.

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Altman, Efrat, i Gil Segal. "The Response Regulator CpxR Directly Regulates Expression of Several Legionella pneumophila icm/dot Components as Well as New Translocated Substrates". Journal of Bacteriology 190, nr 6 (11.01.2008): 1985–96. http://dx.doi.org/10.1128/jb.01493-07.

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ABSTRACT Legionella pneumophila has been shown to utilize the icm/dot type IV secretion system for pathogenesis. This system was shown to be composed of icm/dot complex components and accessory proteins, as well as a large number of translocated substrates. Bioinformatic analysis of the regulatory regions of all the genes revealed that several icm/dot genes, as well as two genes encoding icm/dot translocated substrates, contain the conserved CpxR regulatory element, a regulator that has been shown previously to control the expression of the icmR gene. An experimental analysis, which included a comparison of gene expression in a L. pneumophila wild-type strain and gene expression in a cpxR deletion mutant, construction of mutants with mutations in the CpxR conserved regulatory elements, controlled expression studies, and mobility shift assays, demonstrated the direct relationship between the CpxR regulator and the expression of the genes. Furthermore, genomic analysis identified nine additional genes that contain a putative CpxR regulatory element; five of these genes (two legA genes and three ceg genes) were suggested previously to be putative icm/dot translocated substrates. The three ceg genes identified, which were shown previously to contain a putative PmrA regulatory element, were found here to be regulated by both CpxR and PmrA. The other six genes (two legA genes and four new genes products were found to be regulated by CpxR. Moreover, using the CyaA translocation assay, these nine gene products were found to be translocated into host cells in an Icm/Dot-dependent manner. Our results establish that the CpxR regulator is a fundamental regulator of the icm/dot type IV secretion system in L. pneumophila.

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Kohn, K. W. "Regulatory Genes and Drug Sensitivity". JNCI Journal of the National Cancer Institute 88, nr 18 (18.09.1996): 1255–56. http://dx.doi.org/10.1093/jnci/88.18.1255.

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HE, W., J. LEI, Y. LIU i Y. WANG. "Regulatory Genes of Geldanamycin Biosynthesis". Chinese Journal of Biotechnology 24, nr 5 (maj 2008): 717–22. http://dx.doi.org/10.1016/s1872-2075(08)60036-9.

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Via, Sara. "Regulatory Genes and Reaction Norms". American Naturalist 142, nr 2 (sierpień 1993): 374–78. http://dx.doi.org/10.1086/285545.

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Davis, Meryl A., i Michael J. Hynes. "Regulatory genes in aspergillus nidulans". Trends in Genetics 5 (1989): 14–19. http://dx.doi.org/10.1016/0168-9525(89)90006-1.

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Britton, Candace S., Trevor R. Sorrells i Alexander D. Johnson. "Protein-coding changes preceded cis-regulatory gains in a newly evolved transcription circuit". Science 367, nr 6473 (2.01.2020): 96–100. http://dx.doi.org/10.1126/science.aax5217.

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Changes in both the coding sequence of transcriptional regulators and in the cis-regulatory sequences recognized by these regulators have been implicated in the evolution of transcriptional circuits. However, little is known about how they evolved in concert. We describe an evolutionary pathway in fungi where a new transcriptional circuit (a-specific gene repression by the homeodomain protein Matα2) evolved by coding changes in this ancient regulator, followed millions of years later by cis-regulatory sequence changes in the genes of its future regulon. By analyzing a group of species that has acquired the coding changes but not the cis-regulatory sites, we show that the coding changes became necessary for the regulator’s deeply conserved function, thereby poising the regulator to jump-start formation of the new circuit.

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Bignell, Dawn R. D., Isolde M. Francis, Joanna K. Fyans i Rosemary Loria. "Thaxtomin A Production and Virulence Are Controlled by Several bld Gene Global Regulators in Streptomyces scabies". Molecular Plant-Microbe Interactions® 27, nr 8 (sierpień 2014): 875–85. http://dx.doi.org/10.1094/mpmi-02-14-0037-r.

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Streptomyces scabies is the main causative agent of common scab disease, which leads to significant annual losses to potato growers worldwide. The main virulence factor produced by S. scabies is a phytotoxic secondary metabolite called thaxtomin A, which functions as a cellulose synthesis inhibitor. Thaxtomin A production is controlled by the cluster-situated regulator TxtR, which activates expression of the thaxtomin biosynthetic genes in response to cello-oligosaccharides. Here, we demonstrate that at least five additional regulatory genes are required for wild-type levels of thaxtomin A production and plant pathogenicity in S. scabies. These regulatory genes belong to the bld gene family of global regulators that control secondary metabolism or morphological differentiation in Streptomyces spp. Quantitative reverse-transcriptase polymerase chain reaction showed that expression of the thaxtomin biosynthetic genes was significantly downregulated in all five bld mutants and, in four of these mutants, this downregulation was attributed to the reduction in expression of txtR. Furthermore, all of the mutants displayed reduced expression of other known or predicted virulence genes, suggesting that the bld genes may function as global regulators of virulence gene expression in S. scabies.

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Chang, Yao-Ming, Hsin-Hung Lin, Wen-Yu Liu, Chun-Ping Yu, Hsiang-June Chen, Putu Puja Wartini, Yi-Ying Kao i in. "Comparative transcriptomics method to infer gene coexpression networks and its applications to maize and rice leaf transcriptomes". Proceedings of the National Academy of Sciences 116, nr 8 (4.02.2019): 3091–99. http://dx.doi.org/10.1073/pnas.1817621116.

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Time-series transcriptomes of a biological process obtained under different conditions are useful for identifying the regulators of the process and their regulatory networks. However, such data are 3D (gene expression, time, and condition), and there is currently no method that can deal with their full complexity. Here, we developed a method that avoids time-point alignment and normalization between conditions. We applied it to analyze time-series transcriptomes of developing maize leaves under light–dark cycles and under total darkness and obtained eight time-ordered gene coexpression networks (TO-GCNs), which can be used to predict upstream regulators of any genes in the GCNs. One of the eight TO-GCNs is light-independent and likely includes all genes involved in the development of Kranz anatomy, which is a structure crucial for the high efficiency of photosynthesis in C4 plants. Using this TO-GCN, we predicted and experimentally validated a regulatory cascade upstream of SHORTROOT1, a key Kranz anatomy regulator. Moreover, we applied the method to compare transcriptomes from maize and rice leaf segments and identified regulators of maize C4 enzyme genes and RUBISCO SMALL SUBUNIT2. Our study provides not only a powerful method but also novel insights into the regulatory networks underlying Kranz anatomy development and C4 photosynthesis.

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Kreikemeyer, Bernd, Masanobu Nakata, Thomas Köller, Hendrikje Hildisch, Vassilios Kourakos, Kerstin Standar, Shigetada Kawabata, Michael O. Glocker i Andreas Podbielski. "The Streptococcus pyogenes Serotype M49 Nra-Ralp3 Transcriptional Regulatory Network and Its Control of Virulence Factor Expression from the Novel eno ralp3 epf sagA Pathogenicity Region". Infection and Immunity 75, nr 12 (24.09.2007): 5698–710. http://dx.doi.org/10.1128/iai.00175-07.

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ABSTRACT Many Streptococcus pyogenes (group A streptococcus [GAS]) virulence factor- and transcriptional regulator-encoding genes cluster together in discrete genomic regions. Nra is a central regulator of the FCT region. Previous studies exclusively described Nra as a transcriptional repressor of adhesin and toxin genes. Here transcriptome and proteome analysis of a serotype M49 GAS strain and an isogenic Nra mutant of this strain revealed the complete Nra regulon profile. Nra is active in all growth phases tested, with the largest regulon in the transition phase. Almost exclusively, virulence factor-encoding genes are repressed by Nra; these genes include the GAS pilus operon, the capsule synthesis operon, the cytolysin-mediated translocation system genes, all Mga region core virulence genes, and genes encoding other regulators, like the Ihk/Irr system, Rgg, and two additional RofA-like protein family regulators. Surprisingly, our experiments revealed that Nra additionally acts as a positive regulator, mostly for genes encoding proteins and enzymes with metabolic functions. Epidemiological investigations revealed strong genetic linkage of one particular Nra-repressed regulator, Ralp3 (SPy0735), with a gene encoding Epf (extracellular protein factor from Streptococcus suis). In a serotype-specific fashion, this ralp3 epf gene block is integrated, most likely via transposition, into the eno sagA virulence gene block, which is present in all GAS serotypes. In GAS serotypes M1, M4, M12, M28, and M49 this novel discrete genetic region is therefore designated the eno ralp3 epf sagA (ERES) pathogenicity region. Functional experiments showed that Epf is a novel GAS plasminogen-binding protein and revealed that Ralp3 activity counteracts Nra and MsmR regulatory activity. In addition to the Mga and FCT regions, the ERES region is the third discrete chromosomal pathogenicity region. All of these regions are transcriptionally linked, adding another level of complexity to the known GAS growth phase-dependent regulatory network.

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Greenberg, M. L., P. L. Myers, R. C. Skvirsky i H. Greer. "New positive and negative regulators for general control of amino acid biosynthesis in Saccharomyces cerevisiae". Molecular and Cellular Biology 6, nr 5 (maj 1986): 1820–29. http://dx.doi.org/10.1128/mcb.6.5.1820-1829.1986.

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The biosynthesis of most amino acids in Saccharomyces cerevisiae is coregulated. Starvation for a single amino acid results in the derepression of amino acid biosynthetic enzymes in many unrelated pathways. This phenomenon, known as general control, is mediated by both positive (GCN) and negative (GCD) regulatory genes. In this paper we describe the identification and characterization of several new regulatory genes for this system, GCN6, GCN7, GCN8, GCN9, and GCD5. A mutation in the negative regulator GCD5 was isolated on the basis of its suppression of a gcn2 mutation. The effect of gcd5 is a posttranscriptional increase in histidine biosynthetic enzyme activity. Suppressors of gcd5 which are deficient in derepression were in turn isolated. Eight such mutations, defining four new positive regulatory genes (GCN6 through GCN9), were obtained. These mutations are recessive, confer sensitivity to multiple amino acid analogs, and result in decreased mRNA levels for genes under general control. The GCN6 and GCN7 gene products were shown to be positive regulators for transcription of the GCN4 gene, the most direct-acting positive regulator thus far identified. The interaction of GCN6 and GCN7 with GCN4 is fundamentally different from that of previously isolated GCN genes. It should also be noted that these gcn selections gave a completely different nonoverlapping set of mutations from earlier selections which relied on analog sensitivity. Thus, we may have identified a new class of GCN genes which are functionally distinct from GCN1 through GCN5.

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Greenberg, M. L., P. L. Myers, R. C. Skvirsky i H. Greer. "New positive and negative regulators for general control of amino acid biosynthesis in Saccharomyces cerevisiae." Molecular and Cellular Biology 6, nr 5 (maj 1986): 1820–29. http://dx.doi.org/10.1128/mcb.6.5.1820.

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The biosynthesis of most amino acids in Saccharomyces cerevisiae is coregulated. Starvation for a single amino acid results in the derepression of amino acid biosynthetic enzymes in many unrelated pathways. This phenomenon, known as general control, is mediated by both positive (GCN) and negative (GCD) regulatory genes. In this paper we describe the identification and characterization of several new regulatory genes for this system, GCN6, GCN7, GCN8, GCN9, and GCD5. A mutation in the negative regulator GCD5 was isolated on the basis of its suppression of a gcn2 mutation. The effect of gcd5 is a posttranscriptional increase in histidine biosynthetic enzyme activity. Suppressors of gcd5 which are deficient in derepression were in turn isolated. Eight such mutations, defining four new positive regulatory genes (GCN6 through GCN9), were obtained. These mutations are recessive, confer sensitivity to multiple amino acid analogs, and result in decreased mRNA levels for genes under general control. The GCN6 and GCN7 gene products were shown to be positive regulators for transcription of the GCN4 gene, the most direct-acting positive regulator thus far identified. The interaction of GCN6 and GCN7 with GCN4 is fundamentally different from that of previously isolated GCN genes. It should also be noted that these gcn selections gave a completely different nonoverlapping set of mutations from earlier selections which relied on analog sensitivity. Thus, we may have identified a new class of GCN genes which are functionally distinct from GCN1 through GCN5.

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Yin, Wencheng, Luis Mendoza, Jimena Monzon-Sandoval, Araxi O. Urrutia i Humberto Gutierrez. "Emergence of co-expression in gene regulatory networks". PLOS ONE 16, nr 4 (1.04.2021): e0247671. http://dx.doi.org/10.1371/journal.pone.0247671.

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Transcriptomes are known to organize themselves into gene co-expression clusters or modules where groups of genes display distinct patterns of coordinated or synchronous expression across independent biological samples. The functional significance of these co-expression clusters is suggested by the fact that highly coexpressed groups of genes tend to be enriched in genes involved in common functions and biological processes. While gene co-expression is widely assumed to reflect close regulatory proximity, the validity of this assumption remains unclear. Here we use a simple synthetic gene regulatory network (GRN) model and contrast the resulting co-expression structure produced by these networks with their known regulatory architecture and with the co-expression structure measured in available human expression data. Using randomization tests, we found that the levels of co-expression observed in simulated expression data were, just as with empirical data, significantly higher than expected by chance. When examining the source of correlated expression, we found that individual regulators, both in simulated and experimental data, fail, on average, to display correlated expression with their immediate targets. However, highly correlated gene pairs tend to share at least one common regulator, while most gene pairs sharing common regulators do not necessarily display correlated expression. Our results demonstrate that widespread co-expression naturally emerges in regulatory networks, and that it is a reliable and direct indicator of active co-regulation in a given cellular context.

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Sekurova, Olga N., Trygve Brautaset, Håvard Sletta, Sven E. F. Borgos, Øyvind M. Jakobsen, Trond E. Ellingsen, Arne R. Strøm, Svein Valla i Sergey B. Zotchev. "In Vivo Analysis of the Regulatory Genes in the Nystatin Biosynthetic Gene Cluster of Streptomyces noursei ATCC 11455 Reveals Their Differential Control Over Antibiotic Biosynthesis". Journal of Bacteriology 186, nr 5 (1.03.2004): 1345–54. http://dx.doi.org/10.1128/jb.186.5.1345-1354.2004.

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ABSTRACT Six putative regulatory genes are located at the flank of the nystatin biosynthetic gene cluster in Streptomyces noursei ATCC 11455. Gene inactivation and complementation experiments revealed that nysRI, nysRII, nysRIII, and nysRIV are necessary for efficient nystatin production, whereas no significant roles could be demonstrated for the other two regulatory genes. To determine the in vivo targets for the NysR regulators, chromosomal integration vectors with the xylE reporter gene under the control of seven putative promoter regions upstream of the nystatin structural and regulatory genes were constructed. Expression analyses of the resulting vectors in the S. noursei wild-type strain and regulatory mutants revealed that the four regulators differentially affect certain promoters. According to these analyses, genes responsible for initiation of nystatin biosynthesis and antibiotic transport were the major targets for regulation. Data from cross-complementation experiments showed that nysR genes could in some cases substitute for each other, suggesting a functional hierarchy of the regulators and implying a cascade-like mechanism of regulation of nystatin biosynthesis.

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26

Gomes, Ignatius, Tiffany T. Sharma, Seby Edassery, Noreen Fulton, Brenton G. Mar i Carol A. Westbrook. "Novel transcription factors in human CD34 antigen–positive hematopoietic cells". Blood 100, nr 1 (1.07.2002): 107–19. http://dx.doi.org/10.1182/blood.v100.1.107.

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Abstract Transcription factors (TFs) and the regulatory proteins that control them play key roles in hematopoiesis, controlling basic processes of cell growth and differentiation; disruption of these processes may lead to leukemogenesis. Here we attempt to identify functionally novel and partially characterized TFs/regulatory proteins that are expressed in undifferentiated hematopoietic tissue. We surveyed our database of 15 970 genes/expressed sequence tags (ESTs) representing the normal human CD34+ cells transcriptosome (http://westsun.hema.uic.edu/cd34.html), using the UniGene annotation text descriptor, to identify genes with motifs consistent with transcriptional regulators; 285 genes were identified. We also extracted the human homologues of the TFs reported in the murine stem cell database (SCdb; http://stemcell.princeton.edu/), selecting an additional 45 genes/ESTs. An exhaustive literature search of each of these 330 unique genes was performed to determine if any had been previously reported and to obtain additional characterizing information. Of the resulting gene list, 106 were considered to be potential TFs. Overall, the transcriptional regulator dataset consists of 165 novel or poorly characterized genes, including 25 that appeared to be TFs. Among these novel and poorly characterized genes are a cell growth regulatory with ring finger domain protein (CGR19, Hs.59106), an RB-associated CRAB repressor (RBAK, Hs.7222), a death-associated transcription factor 1 (DATF1, Hs.155313), and a p38-interacting protein (P38IP, Hs. 171185). The identification of these novel and partially characterized potential transcriptional regulators adds a wealth of information to understanding the molecular aspects of hematopoiesis and hematopoietic disorders.

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27

Saïd-Salim, B., P. M. Dunman, F. M. McAleese, D. Macapagal, E. Murphy, P. J. McNamara, S. Arvidson, T. J. Foster, S. J. Projan i B. N. Kreiswirth. "Global Regulation of Staphylococcus aureus Genes by Rot". Journal of Bacteriology 185, nr 2 (15.01.2003): 610–19. http://dx.doi.org/10.1128/jb.185.2.610-619.2003.

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ABSTRACT Staphylococcus aureus produces a wide array of cell surface and extracellular proteins involved in virulence. Expression of these virulence factors is tightly controlled by numerous regulatory loci, including agr, sar, sigB, sae, and arl, as well as by a number of proteins with homology to SarA. Rot (repressor of toxins), a SarA homologue, was previously identified in a library of transposon-induced mutants created in an agr-negative strain by screening for restored protease and alpha-toxin. To date, all of the SarA homologues have been shown to act as global regulators of virulence genes. Therefore, we investigated the extent of transcriptional regulation of staphylococcal genes by Rot. We compared the transcriptional profile of a rot agr double mutant to that of its agr parental strain by using custom-made Affymetrix GeneChips. Our findings indicate that Rot is not only a repressor but a global regulator with both positive and negative effects on the expression of S. aureus genes. Our data also indicate that Rot and agr have opposing effects on select target genes. These results provide further insight into the role of Rot in the regulatory cascade of S. aureus virulence gene expression.

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Bačovský, Václav, Radim Čegan, Eva Tihlaříková, Vilém Neděla, Vojtěch Hudzieczek, Lubomír Smrža, Tomáš Janíček, Vladimír Beneš i Roman Hobza. "Chemical genetics in Silene latifolia elucidate regulatory pathways involved in gynoecium development". Journal of Experimental Botany 73, nr 8 (19.01.2022): 2354–68. http://dx.doi.org/10.1093/jxb/erab538.

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Abstract Dioecious plants possess diverse sex determination systems and unique mechanisms of reproductive organ development; however, little is known about how sex-linked genes shape the expression of regulatory cascades that lead to developmental differences between sexes. In Silene latifolia, a dioecious plant with stable dimorphism in floral traits, early experiments suggested that female-regulator genes act on the factors that determine the boundaries of the flower whorls. To identify these regulators, we sequenced the transcriptome of male flowers with fully developed gynoecia, induced by rapid demethylation in the parental generation. Eight candidates were found to have a positive role in gynoecium promotion, floral organ size, and whorl boundary, and affect the expression of class B MADS-box flower genes. To complement our transcriptome analysis, we closely examined the floral organs in their native state using field emission environmental scanning electron microscopy, and examined the differences between females and androhermaphrodites in their placenta and ovule organization. Our results reveal the regulatory pathways potentially involved in sex-specific flower development in the classical model of dioecy, S. latifolia. These pathways include previously hypothesized and unknown female-regulator genes that act on the factors that determine the flower boundaries, and a negative regulator of anther development, SUPERMAN-like (SlSUP).

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29

Pulsawat, Nattika, Shigeru Kitani, Eriko Fukushima i Takuya Nihira. "Hierarchical control of virginiamycin production in Streptomyces virginiae by three pathway-specific regulators: VmsS, VmsT and VmsR". Microbiology 155, nr 4 (1.04.2009): 1250–59. http://dx.doi.org/10.1099/mic.0.022467-0.

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Two regulatory genes encoding a Streptomyces antibiotic regulatory protein (vmsS) and a response regulator (vmsT) of a bacterial two-component signal transduction system are present in the left-hand region of the biosynthetic gene cluster of the antibiotic virginiamycin, which is composed of virginiamycin M (VM) and virginiamycin S (VS), in Streptomyces virginiae. Disruption of vmsS abolished both VM and VS biosynthesis, with drastic alteration of the transcriptional profile for virginiamycin biosynthetic genes, whereas disruption of vmsT resulted in only a loss of VM biosynthesis, suggesting that vmsS is a pathway-specific regulator for both VM and VS biosynthesis, and that vmsT is a pathway-specific regulator for VM biosynthesis alone. Gene expression profiles determined by semiquantitative RT-PCR on the virginiamycin biosynthetic gene cluster demonstrated that vmsS controls the biosynthetic genes for VM and VS, and vmsT controls unidentified gene(s) of VM biosynthesis located outside the biosynthetic gene cluster. In addition, transcriptional analysis of a deletion mutant of vmsR located in the clustered regulatory region in the virginiamycin cluster (and which also acts as a SARP-family activator for both VM and VS biosynthesis) indicated that the expression of vmsS and vmsT is under the control of vmsR, and vmsR also contributes to the expression of VM and VS biosynthetic genes, independent of vmsS and vmsT. Therefore, coordinated virginiamycin biosynthesis is controlled by three pathway-specific regulators which hierarchically control the expression of the biosynthetic gene cluster.

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30

Casper-Lindley, Catharina, i Fitnat H. Yildiz. "VpsT Is a Transcriptional Regulator Required for Expression of vps Biosynthesis Genes and the Development of Rugose Colonial Morphology in Vibrio cholerae O1 El Tor". Journal of Bacteriology 186, nr 5 (1.03.2004): 1574–78. http://dx.doi.org/10.1128/jb.186.5.1574-1578.2004.

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ABSTRACT Vibrio cholerae switches between smooth and rugose colonial variants. The rugose variant produces more vibrio polysaccharides (VPSEl Tor) and forms well-developed biofilms. Both phenotypes depend on expression of vps biosynthesis genes. We identified a positive transcriptional regulator of vps gene expression, VpsT, which is homologous to response regulators of two-component regulatory systems. Disruption of vpsT in the rugose variant yields smooth colonies, prevents formation of mature biofilms, and decreases vps gene expression. The interaction between VpsT and VpsR, a previously identified positive regulator of vps genes, was also investigated.

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31

Didych, D. A., D. V. Tyulkina, V. V. Pleshkan, I. V. Alekseenko i E. D. Sverdlov. "Are super-enhancers regulators of regulatory genes of development and cancer?" Molecular Biology 49, nr 6 (listopad 2015): 818–24. http://dx.doi.org/10.1134/s0026893315060059.

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32

Meibom, Karin L., Anna-Lena Forslund, Kerstin Kuoppa, Khaled Alkhuder, Iharilalao Dubail, Marion Dupuis, Åke Forsberg i Alain Charbit. "Hfq, a Novel Pleiotropic Regulator of Virulence-Associated Genes in Francisella tularensis". Infection and Immunity 77, nr 5 (17.02.2009): 1866–80. http://dx.doi.org/10.1128/iai.01496-08.

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ABSTRACT Francisella tularensis is a highly infectious pathogen that infects animals and humans, causing tularemia. The ability to replicate within macrophages is central for virulence and relies on expression of genes located in the Francisella pathogenicity island (FPI), as well as expression of other genes. Regulation of FPI-encoded virulence gene expression in F. tularensis involves at least four regulatory proteins and is not fully understood. Here we studied the RNA-binding protein Hfq in F. tularensis and particularly the role that it plays as a global regulator of gene expression in stress tolerance and pathogenesis. We demonstrate that Hfq promotes resistance to several cellular stresses (including osmotic and membrane stresses). Furthermore, we show that Hfq is important for the ability of the F. tularensis vaccine strain LVS to induce disease and persist in organs of infected mice. We also demonstrate that Hfq is important for stress tolerance and full virulence in a virulent clinical isolate of F. tularensis, FSC200. Finally, microarray analyses revealed that Hfq regulates expression of numerous genes, including genes located in the FPI. Strikingly, Hfq negatively regulates only one of two divergently expressed putative operons in the FPI, in contrast to the other known regulators, which regulate the entire FPI. Hfq thus appears to be a new pleiotropic regulator of virulence in F. tularensis, acting mostly as a repressor, in contrast to the other regulators identified so far. Moreover, the results obtained suggest a novel regulatory mechanism for a subset of FPI genes.

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33

Stewart, Alexander J., i Joshua B. Plotkin. "The evolution of complex gene regulation by low-specificity binding sites". Proceedings of the Royal Society B: Biological Sciences 280, nr 1768 (7.10.2013): 20131313. http://dx.doi.org/10.1098/rspb.2013.1313.

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Requirements for gene regulation vary widely both within and among species. Some genes are constitutively expressed, whereas other genes require complex regulatory control. Transcriptional regulation is often controlled by a module of multiple transcription factor binding sites that, in combination, mediate the expression of a target gene. Here, we study how such regulatory modules evolve in response to natural selection. Using a population-genetic model, we show that complex regulatory modules which contain a larger number of binding sites must employ binding motifs that are less specific, on average, compared with smaller regulatory modules. This effect is extremely general, and it holds regardless of the selected binding logic that a module experiences. We attribute this phenomenon to the inability of stabilizing selection to maintain highly specific sites in large regulatory modules. Our analysis helps to explain broad empirical trends in the Saccharomyces cerevisiae regulatory network: those genes with a greater number of distinct transcriptional regulators feature less-specific binding motifs, compared with genes with fewer regulators. Our results also help to explain empirical trends in module size and motif specificity across species, ranging from prokaryotes to single-cellular and multi-cellular eukaryotes.

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34

Sanda, Takaomi, Lee N. Lawton, M. Inmaculada Barrasa, Zi Peng Fan, Yebin Ahn, Richard Young i A. Thomas Look. "Core Transcriptional Regulatory Circuit Controlled by the TAL1 Complex in T-Cell Acute Lymphoblastic Leukemia",. Blood 118, nr 21 (18.11.2011): 3453. http://dx.doi.org/10.1182/blood.v118.21.3453.3453.

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Abstract Abstract 3453 Aberrant expression of TAL1 is one of the most frequent abnormalities in T-cell acute lymphoblastic leukemia (T-ALL), yet little is known about the transcriptional network controlled by this oncogenic transcription factor, posing a major obstacle to understanding T-ALL pathogenesis. Here we identify the core transcriptional regulatory circuit controlled by TAL1 and its regulatory partners HEB, E2A, GATA3 and RUNX1 in T-ALL cells. We determined direct transcriptional targets of TAL1 and its regulatory partners by ChIP-seq analysis, and found that TAL1 binds to the majority of HEB- and E2A-enriched regions and that these commonly bound regions are frequently overlapping with the GATA3- and RUNX1-enriched regions. We found that TAL1 forms an interconnected auto-regulatory loop with its partners, which likely contribute to the sustained upregulation of its direct target genes. TAL1 core regulatory circuit activates genes involved in T-cell development and hematopoesis. Microarray gene expression analysis revealed that TAL1 and GATA3 predominantly act as positive regulators of the expression of their direct target genes in T-ALL. Importantly, we found the MYB oncogenic transcription factor is directly activated by the TAL1 complex and positively regulates many of the same target genes, thus forming a feed-forward positive regulatory loop that further promotes the TAL1-regulated oncogenic program. Moreover, we found that a specific subset of TAL1 target genes are oppositely regulated by TAL1 and its obligate partner proteins E2A and HEB, uncovering a leukemogenic pattern that previously emerged from studies in murine models. These findings underscore the importance of TAL1 as a critical regulator of an aberrant gene expression program in T-ALL, and indicate how these networks maintain the malignant state in thymocytes. Disclosures: No relevant conflicts of interest to declare.

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35

Hill, Robert E., i Laura A. Lettice. "Alterations to the remote control of Shh gene expression cause congenital abnormalities". Philosophical Transactions of the Royal Society B: Biological Sciences 368, nr 1620 (19.06.2013): 20120357. http://dx.doi.org/10.1098/rstb.2012.0357.

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Multi-species conserved non-coding elements occur in the vertebrate genome and are clustered in the vicinity of developmentally regulated genes. Many are known to act as cis -regulators of transcription and may reside at long distances from the genes they regulate. However, the relationship of conserved sequence to encoded regulatory information and indeed, the mechanism by which these contribute to long-range transcriptional regulation is not well understood. The ZRS, a highly conserved cis -regulator, is a paradigm for such long-range gene regulation. The ZRS acts over approximately 1 Mb to control spatio-temporal expression of Shh in the limb bud and mutations within it result in a number of limb abnormalities, including polydactyly, tibial hypoplasia and syndactyly. We describe the activity of this developmental regulator and discuss a number of mechanisms by which regulatory mutations in this enhancer function to cause congenital abnormalities.

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36

Panijel, Mary, Laura Chalupowicz, Guido Sessa, Shulamit Manulis-Sasson i Isaac Barash. "Global Regulatory Networks Control the Hrp Regulon of the Gall-Forming Bacterium Pantoea agglomerans pv. gypsophilae". Molecular Plant-Microbe Interactions® 26, nr 9 (wrzesień 2013): 1031–43. http://dx.doi.org/10.1094/mpmi-04-13-0097-r.

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Gall formation by Pantoea agglomerans pv. gypsophilae is dependent on the hypersensitive response and pathogenicity (hrp) system. Previous studies demonstrated that PagR and PagI, regulators of the quorum-sensing system, induce expression of the hrp regulatory cascade (i.e., hrpXY, hrpS, and hrpL) that activates the HrpL regulon. Here, we isolated the genes of the Gac/Rsm global regulatory pathway (i.e., gacS, gacA, rsmB, and csrD) and of the post-transcriptional regulator rsmA. Our results demonstrate that PagR and PagI also upregulate expression of the Gac/Rsm pathway. PagR acts as a transcriptional activator of each of the hrp regulatory genes and gacA in a N-butanoyl-L-homoserine lactone-dependent manner as shown by gel shift experiments. Mutants of the Gac/Rsm genes or overexpression of rsmA significantly reduced Pantoea agglomerans virulence and colonization of gypsophila. Overexpression of rsmB sRNA abolished gall formation, colonization, and hypersensitive reaction on nonhost plants and prevented transcription of the hrp regulatory cascade, indicating a lack of functional type III secretion system. Expression of rsmB sRNA in the background of the csrD null mutant suggests that CsrD may act as a safeguard for preventing excessive production of rsmB sRNA. Results presented indicate that the hrp regulatory cascade is controlled directly by PagR and indirectly by RsmA, whereas deficiency in RsmA activity is epistatic to PagR induction.

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37

Kendall, Sharon L., Farahnaz Movahedzadeh, Andreas Wietzorrek i Neil G. Stoker. "Microarray Analysis of Bacterial Gene Expression: Towards the Regulome". Comparative and Functional Genomics 3, nr 4 (2002): 352–54. http://dx.doi.org/10.1002/cfg.193.

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Microarray technology allows co-regulated genes to be identified. In order to identify genes that are controlled by specific regulators, gene expression can be compared in mutant and wild-type bacteria. However, there are a number of pitfalls with this approach; in particular, the regulator may not be active under the conditions in which the wild-type strain is cultured. Once co-regulated genes have been identified, proteinbinding motifs can be identified. By combining these data with a map of promoters, or operons (the operome), the regulatory networks in the cell (the regulome) can start to be built up.

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38

Hoskins, Jason W., Charles C. Chung, Aidan O’Brien, Jun Zhong, Katelyn Connelly, Irene Collins, Jianxin Shi i Laufey T. Amundadottir. "Inferred expression regulator activities suggest genes mediating cardiometabolic genetic signals". PLOS Computational Biology 17, nr 11 (18.11.2021): e1009563. http://dx.doi.org/10.1371/journal.pcbi.1009563.

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Expression QTL (eQTL) analyses have suggested many genes mediating genome-wide association study (GWAS) signals but most GWAS signals still lack compelling explanatory genes. We have leveraged an adipose-specific gene regulatory network to infer expression regulator activities and phenotypic master regulators (MRs), which were used to detect activity QTLs (aQTLs) at cardiometabolic trait GWAS loci. Regulator activities were inferred with the VIPER algorithm that integrates enrichment of expected expression changes among a regulator’s target genes with confidence in their regulator-target network interactions and target overlap between different regulators (i.e., pleiotropy). Phenotypic MRs were identified as those regulators whose activities were most important in predicting their respective phenotypes using random forest modeling. While eQTLs were typically more significant than aQTLs in cis, the opposite was true among candidate MRs in trans. Several GWAS loci colocalized with MR trans-eQTLs/aQTLs in the absence of colocalized cis-QTLs. Intriguingly, at the 1p36.1 BMI GWAS locus the EPHB2 cis-aQTL was stronger than its cis-eQTL and colocalized with the GWAS signal and 35 BMI MR trans-aQTLs, suggesting the GWAS signal may be mediated by effects on EPHB2 activity and its downstream effects on a network of BMI MRs. These MR and aQTL analyses represent systems genetic methods that may be broadly applied to supplement standard eQTL analyses for suggesting molecular effects mediating GWAS signals.

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39

Sakuragi, Junichi, Hiroyuki Sakai i Akio Adachi. "Exchangeability of HIV/SIV regulatory genes." Uirusu 42, nr 2 (1992): 133–43. http://dx.doi.org/10.2222/jsv.42.133.

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Ishii, Naoaki. "The Regulatory Genes of Nematode Lifespan." Nippon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics 36, nr 9 (1999): 613–19. http://dx.doi.org/10.3143/geriatrics.36.613.

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Wray, Gregory A., i Christopher J. Lowe. "Developmental Regulatory Genes and Echinoderm Evolution". Systematic Biology 49, nr 1 (1.01.2000): 28–51. http://dx.doi.org/10.1080/10635150050207375.

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42

Bolt, Christopher Chase, i Denis Duboule. "The regulatory landscapes of developmental genes". Development 147, nr 3 (1.02.2020): dev171736. http://dx.doi.org/10.1242/dev.171736.

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DAVIES, PETER, i NEIL K. RUSHMERE. "Regulatory regions of androgen-responsive genes". Biochemical Society Transactions 16, nr 5 (1.10.1988): 695–98. http://dx.doi.org/10.1042/bst0160695.

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Pérez-Morales, Deyanira, Jessica Nava-Galeana, Roberto Rosales-Reyes, Paige Teehan, Helen Yakhnin, Erika I. Melchy-Pérez, Yvonne Rosenstein, Miguel A. De la Cruz, Paul Babitzke i Víctor H. Bustamante. "An incoherent feedforward loop formed by SirA/BarA, HilE and HilD is involved in controlling the growth cost of virulence factor expression by Salmonella Typhimurium". PLOS Pathogens 17, nr 5 (28.05.2021): e1009630. http://dx.doi.org/10.1371/journal.ppat.1009630.

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An intricate regulatory network controls the expression of Salmonella virulence genes. The transcriptional regulator HilD plays a central role in this network by controlling the expression of tens of genes mainly required for intestinal colonization. Accordingly, the expression/activity of HilD is highly regulated by multiple factors, such as the SirA/BarA two-component system and the Hcp-like protein HilE. SirA/BarA positively regulates translation of hilD mRNA through a regulatory cascade involving the small RNAs CsrB and CsrC, and the RNA-binding protein CsrA, whereas HilE inhibits HilD activity by protein-protein interaction. In this study, we show that SirA/BarA also positively regulates translation of hilE mRNA through the same mentioned regulatory cascade. Thus, our results reveal a paradoxical regulation exerted by SirA/BarA-Csr on HilD, which involves simultaneous opposite effects, direct positive control and indirect negative control through HilE. This kind of regulation is called an incoherent type-1 feedforward loop (I1-FFL), which is a motif present in certain regulatory networks and represents a complex biological problem to decipher. Interestingly, our results, together with those from a previous study, indicate that HilE, the repressor component of the I1-FFL reported here (I1-FFLSirA/BarA-HilE-HilD), is required to reduce the growth cost imposed by the expression of the genes regulated by HilD. Moreover, we and others found that HilE is necessary for successful intestinal colonization by Salmonella. Thus, these findings support that I1-FFLSirA/BarA-HilE-HilD cooperates to control the precise amount and activity of HilD, for an appropriate balance between the growth cost and the virulence benefit generated by the expression of the genes induced by this regulator. I1-FFLSirA/BarA-HilE-HilD represents a complex regulatory I1-FFL that involves multiple regulators acting at distinct levels of gene expression, as well as showing different connections to the rest of the regulatory network governing Salmonella virulence.

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45

Torres, María J., Emilio Bueno, Socorro Mesa, Eulogio J. Bedmar i María J. Delgado. "Emerging complexity in the denitrification regulatory network of Bradyrhizobium japonicum". Biochemical Society Transactions 39, nr 1 (19.01.2011): 284–88. http://dx.doi.org/10.1042/bst0390284.

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Bradyrhizobium japonicum is a Gram-negative soil bacterium symbiotically associated with soya bean plants, which is also able to denitrify under free-living and symbiotic conditions. In B. japonicum, the napEDABC, nirK, norCBQD and nosRZDYFLX genes which encode reductases for nitrate, nitrite, nitric oxide and nitrous oxide respectively are required for denitrification. Similar to many other denitrifiers, expression of denitrification genes in B. japonicum requires both oxygen limitation and the presence of nitrate or a derived nitrogen oxide. In B. japonicum, a sophisticated regulatory network consisting of two linked regulatory cascades co-ordinates the expression of genes required for microaerobic respiration (the FixLJ/FixK2 cascade) and for nitrogen fixation (the RegSR/NifA cascade). The involvement of the FixLJ/FixK2 regulatory cascade in the microaerobic induction of the denitrification genes is well established. In addition, the FNR (fumarase and nitrate reduction regulator)/CRP(cAMP receptor protein)-type regulator NnrR expands the FixLJ/FixK2 regulatory cascade by an additional control level. A role for NifA is suggested in this process by recent experiments which have shown that it is required for full expression of denitrification genes in B. japonicum. The present review summarizes the current understanding of the regulatory network of denitrification in B. japonicum.

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46

Weber, Harald, Tino Polen, Johanna Heuveling, Volker F. Wendisch i Regine Hengge. "Genome-Wide Analysis of the General Stress Response Network in Escherichia coli: σS-Dependent Genes, Promoters, and Sigma Factor Selectivity". Journal of Bacteriology 187, nr 5 (1.03.2005): 1591–603. http://dx.doi.org/10.1128/jb.187.5.1591-1603.2005.

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ABSTRACT The σS (or RpoS) subunit of RNA polymerase is the master regulator of the general stress response in Escherichia coli. While nearly absent in rapidly growing cells, σS is strongly induced during entry into stationary phase and/or many other stress conditions and is essential for the expression of multiple stress resistances. Genome-wide expression profiling data presented here indicate that up to 10% of the E. coli genes are under direct or indirect control of σS and that σS should be considered a second vegetative sigma factor with a major impact not only on stress tolerance but on the entire cell physiology under nonoptimal growth conditions. This large data set allowed us to unequivocally identify a σS consensus promoter in silico. Moreover, our results suggest that σS-dependent genes represent a regulatory network with complex internal control (as exemplified by the acid resistance genes). This network also exhibits extensive regulatory overlaps with other global regulons (e.g., the cyclic AMP receptor protein regulon). In addition, the global regulatory protein Lrp was found to affect σS and/or σ70 selectivity of many promoters. These observations indicate that certain modules of the σS-dependent general stress response can be temporarily recruited by stress-specific regulons, which are controlled by other stress-responsive regulators that act together with σ70 RNA polymerase. Thus, not only the expression of genes within a regulatory network but also the architecture of the network itself can be subject to regulation.

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47

Wang, Dong, Haiying Xue, Yiwen Wang, Ruochun Yin, Fang Xie i Li Luo. "The Sinorhizobium melilotintrXGene Is Involved in Succinoglycan Production, Motility, and Symbiotic Nodulation on Alfalfa". Applied and Environmental Microbiology 79, nr 23 (13.09.2013): 7150–59. http://dx.doi.org/10.1128/aem.02225-13.

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ABSTRACTRhizobia establish a symbiotic relationship with their host legumes to induce the formation of nitrogen-fixing nodules. This process is regulated by many rhizobium regulators, including some two-component regulatory systems (TCSs). NtrY/NtrX, a TCS that was first identified inAzorhizobium caulinodans, is required for free-living nitrogen metabolism and symbiotic nodulation onSesbania rostrata. However, its functions in a typical rhizobium such asSinorhizobium melilotiremain unclear. Here we found that theS. melilotiresponse regulator NtrX but not the histidine kinase NtrY is involved in the regulation of exopolysaccharide production, motility, and symbiosis with alfalfa. A plasmid insertion mutant ofntrXformed mucous colonies, which overproduced succinoglycan, an exopolysaccharide, by upregulating its biosynthesis genes. This mutant also exhibited motility defects due to reduced flagella and decreased expression of flagellins and regulatory genes. The regulation is independent of the known regulatory systems of ExoR/ExoS/ChvI, EmmABC, and ExpR. Alfalfa plants inoculated with thentrXmutant were small and displayed symptoms of nitrogen starvation. Interestingly, the deletion mutant ofntrYshowed a phenotype similar to that of the parent strain. These findings demonstrate that theS. melilotiNtrX is a new regulator of succinoglycan production and motility that is not genetically coupled with NtrY.

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Veyrier, Frédéric, Battouli Saïd-Salim i Marcel A. Behr. "Evolution of the Mycobacterial SigK Regulon". Journal of Bacteriology 190, nr 6 (18.01.2008): 1891–99. http://dx.doi.org/10.1128/jb.01452-07.

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ABSTRACT Previous studies have established that members of the Mycobacterium tuberculosis complex exhibit variable production of the antigenic proteins MPT70 and MPT83 due to mutations in their positive regulator, SigK (sigma factor K), and their negative regulator, RskA (regulator of sigma K). To further understand this highly specific SigK-controlled regulon, we have undertaken evolutionary studies to determine the presence of homologues of SigK-regulated genes in other organisms and to predict its transcriptional network. Evolutionary analysis indicates that the positive and negative regulators are conserved across many organisms, but that the genes under their control are variable. Moreover, the addition, loss, and movement of various genes in the mpt70/83 locus suggest that these genes are unlikely to be cotranscribed. To test predictions from sequence analysis, we have used promoter luciferase fusions and Northern blots to show that the majority of genes in this locus have their own promoters, of which a subset are SigK regulated (mpt83, dipZ, mpt70, and Rv0449c). Next, we have shown that the intracellular inducibility of mpt70 and mpt83 is a conserved property, shared between M. tuberculosis and Mycobacterium marinum. In addition, we have shown that SigK and RskA from an environmental mycobacterium isolate (M. gilvum PYR-GCK) complemented the regulatory activity of M. tuberculosis ΔsigK rskA. Together, our data indicate that the regulatory system SigK/RskA is conserved across the Mycobacterium genus, whereas the regulon under its control varies considerably across species.

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Kajfasz, Jessica K., Isamar Rivera-Ramos, Kathleen Scott-Anne, Stacy Gregoire, Jacqueline Abranches i José A. Lemos. "Transcription of Oxidative Stress Genes Is Directly Activated by SpxA1 and, to a Lesser Extent, by SpxA2 in Streptococcus mutans". Journal of Bacteriology 197, nr 13 (20.04.2015): 2160–70. http://dx.doi.org/10.1128/jb.00118-15.

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ABSTRACTThe SpxA1 and SpxA2 (formerly SpxA and SpxB) transcriptional regulators ofStreptococcus mutansare members of a highly conserved family of proteins found inFirmicutes, and they were previously shown to activate oxidative stress responses. In this study, we showed that SpxA1 exerts substantial positive regulatory influence over oxidative stress genes following exposure to H2O2, while SpxA2 appears to have a secondary regulatory role.In vitrotranscription (IVT) assays using purified SpxA1 and/or SpxA2 showed that SpxA1 and, less often, SpxA2 directly activate transcription of some of the major oxidative stress genes. Addition of equimolar concentrations of SpxA1 and SpxA2 to the IVT reactions neither enhanced transcription of the tested genes nor disrupted the dominant role of SpxA1. Substitution of a conserved glycine residue (G52) present in both Spx proteins by arginine (SpxG52R) resulted in strains that phenocopied the Δspxstrains. Moreover, addition of purified SpxA1G52Rcompletely failed to activate transcription ofahpC,sodA, andtpx, further confirming that the G52 residue is critical for Spx functionality.IMPORTANCEStreptococcus mutansis a pathogen associated with the formation of dental caries in humans. Within the oral cavity,S. mutansroutinely encounters oxidative stress. Our previous data revealed that two regulatory proteins, SpxA1 and SpxA2 (formerly SpxA and SpxB), bear high homology to the Spx regulator that has been characterized as a critical activator of oxidative stress genes inBacillus subtilis. In this report, we prove that Spx proteins ofS. mutansdirectly activate transcription of genes involved in the oxidative stress response, though SpxA1 appears to have a more dominant role than SpxA2. Therefore, the Spx regulators play a critical role in the ability ofS. mutansto thrive within the oral cavity.

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Zhao, Yanwei, Zhenxing Wang, Xizi Wang, Xiaodong Jia i Mingjun Li. "Transcription Factors and MiRNAs Regulate the Mechanism of Drug Resistance in Oesophageal Cancer". Cancer Plus 4, nr 2 (31.05.2022): 16. http://dx.doi.org/10.18063/cp.v4i2.367.

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The presence of drug resistance can lead to differences in treatment outcomes among patients using the same drug. Therefore, identification of key biological markers associated with drug resistance can help clinicians to quickly select the appropriate drug to prolong the survival time of patients, and it is important for drug development and detailed study of the drug’s mechanism of action. Firstly, we screened different drug resistance and sensitive cell lines in esophageal cancer cell lines to find different drug resistance related genes, and annotated these calculated drug resistance related genes into the transcriptional regulatory network we constructed. The regulatory relationships within this transcriptional regulatory network were all experimentally confirmed and further filtered by real esophageal cancer data to identify drug resistance related modules and key regulators. Thirteen drug resistance-associated modules were identified, each containing 1-6 drug resistance-associated key regulators. Among them, transcription factors SP1, has-miR-21-5p and hsa-miR-1-5p play key regulatory roles in the resistance modules of various drugs, and they regulate drug resistance-associated differentially expressed genes through one-step or multi-step regulatory relationships. Key transcription factors and miRNA in the transcriptional regulatory network that regulate drug resistance-associated genes can be used as potential biomarkers to identify drug resistance to the corresponding drugs in tumor patients.

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