Interacting regulatory networks in the facultative photosynthetic bacterium, Rhodobacter sphaeroides 2.4.1

2005 ◽  
Vol 33 (1) ◽  
pp. 51-55 ◽  
Author(s):  
S. Kaplan ◽  
J. Eraso ◽  
J.H. Roh
Keyword(s):  
Gene Expression ◽  
Rhodobacter Sphaeroides ◽  
Regulatory Networks ◽  
Regulatory System ◽  
Photosynthetic Bacterium ◽  
Regulatory Elements ◽  
Terminal Oxidase ◽  
Anaerobic Conditions ◽  
Photosynthetic Membrane ◽  
Two Component

Regulation of photosynthetic membrane synthesis in Rhodobacter sphaeroides 2.4.1 is dependent on the interactions of numerous regulatory elements, with two of the most important being the cbb3 terminal oxidase and the PrrBAC two-component regulatory system. Here, we reveal that the cbb3 terminal oxidase possesses extensive, additional regulatory activities under anaerobic conditions, and that the PrrBAC system is further involved in the regulation of the expression of more than 20% of the R. sphaeroides genome under anaerobic conditions, extending well beyond functions related to redox gene expression.

scholarly journals Role of the fnrL Gene in Photosystem Gene Expression and Photosynthetic Growth of Rhodobacter sphaeroides 2.4.1

1998 ◽  
Vol 180 (6) ◽  
pp. 1496-1503 ◽  
Author(s):  
Jill H. Zeilstra-Ryalls ◽  
Samuel Kaplan
Keyword(s):  
Gene Expression ◽  
Rhodobacter Sphaeroides ◽  
Target Genes ◽  
Regulatory System ◽  
Regulatory Elements ◽  
Oxygen Control ◽  
Absolute Requirement ◽  
Photosynthesis Genes ◽  
Operon Expression

ABSTRACT Anoxygenic photosynthetic growth of Rhodobacter sphaeroides 2.4.1 requires a functional fnrL gene, which encodes the anaerobic regulator, FnrL. Using transcriptional fusions to the puc operon in which the upstream FNR consensus-like sequence is either present or absent, we obtained results that suggest that FnrL has both a direct and an indirect role in puc operon expression. In addition to FnrL, several other factors, including the two-component Prr regulatory system and the transcriptional repressor PpsR, are known to mediate oxygen control of photosynthesis gene expression in this organism. Therefore, we examined the relationship between FnrL and these other regulatory elements. Our results indicate that while mutations of prror ppsR can lead to an increase in expression of some photosynthesis genes under aerobic and anaerobic conditions, regardless of the presence or absence of FnrL, there remains an absolute requirement for a functional fnrL gene for photosynthetic growth. We examined the potential role(s) of FnrL in photosynthetic growth by considering several target genes which may be required for this growth mode.

scholarly journals Tailoring Cardiac Synthetic Transcriptional Modulation Towards Precision Medicine

2022 ◽  
Vol 8 ◽  
Author(s):  
Eric Schoger ◽  
Sara Lelek ◽  
Daniela Panáková ◽  
Laura Cecilia Zelarayán
Keyword(s):  
Gene Expression ◽  
Precision Medicine ◽  
Single Cell ◽  
Regulatory Networks ◽  
Transcriptional Control ◽  
Regulatory Elements ◽  
Comprehensive Overview ◽  
Endogenous Gene ◽  
Cell Technologies ◽  
Organ Systems

Molecular and genetic differences between individual cells within tissues underlie cellular heterogeneities defining organ physiology and function in homeostasis as well as in disease states. Transcriptional control of endogenous gene expression has been intensively studied for decades. Thanks to a fast-developing field of single cell genomics, we are facing an unprecedented leap in information available pertaining organ biology offering a comprehensive overview. The single-cell technologies that arose aided in resolving the precise cellular composition of many organ systems in the past years. Importantly, when applied to diseased tissues, the novel approaches have been immensely improving our understanding of the underlying pathophysiology of common human diseases. With this information, precise prediction of regulatory elements controlling gene expression upon perturbations in a given cell type or a specific context will be realistic. Simultaneously, the technological advances in CRISPR-mediated regulation of gene transcription as well as their application in the context of epigenome modulation, have opened up novel avenues for targeted therapy and personalized medicine. Here, we discuss the fast-paced advancements during the recent years and the applications thereof in the context of cardiac biology and common cardiac disease. The combination of single cell technologies and the deep knowledge of fundamental biology of the diseased heart together with the CRISPR-mediated modulation of gene regulatory networks will be instrumental in tailoring the right strategies for personalized and precision medicine in the near future. In this review, we provide a brief overview of how single cell transcriptomics has advanced our knowledge and paved the way for emerging CRISPR/Cas9-technologies in clinical applications in cardiac biomedicine.

scholarly journals Synthetic gene regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae

2019 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Expression Control ◽  
Gene Expression Control

AbstractStreptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND and IMPLY gates. Finally, we demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.

scholarly journals FlhF and Its GTPase Activity Are Required for Distinct Processes in Flagellar Gene Regulation and Biosynthesis in Campylobacter jejuni

2009 ◽  
Vol 191 (21) ◽  
pp. 6602-6611 ◽  
Author(s):  
Murat Balaban ◽  
Stephanie N. Joslin ◽  
David R. Hendrixson
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Campylobacter Jejuni ◽  
Regulatory System ◽  
Flagellar Gene ◽  
Gtpase Activity ◽  
Gtp Hydrolysis ◽  
Genetic Analyses ◽  
Flagellar Biosynthesis ◽  
Two Component

ABSTRACT FlhF proteins are putative GTPases that are often necessary for one or more steps in flagellar organelle development in polarly flagellated bacteria. In Campylobacter jejuni, FlhF is required for σ54-dependent flagellar gene expression and flagellar biosynthesis, but how FlhF influences these processes is unknown. Furthermore, the GTPase activity of any FlhF protein and the requirement of this speculated activity for steps in flagellar biosynthesis remain uncharacterized. We show here that C. jejuni FlhF hydrolyzes GTP, indicating that these proteins are GTPases. C. jejuni mutants producing FlhF proteins with reduced GTPase activity were not severely defective for σ54-dependent flagellar gene expression, unlike a mutant lacking FlhF. Instead, these mutants had a propensity to lack flagella or produce flagella in improper numbers or at nonpolar locations, indicating that GTP hydrolysis by FlhF is required for proper flagellar biosynthesis. Additional studies focused on elucidating a possible role for FlhF in σ54-dependent flagellar gene expression were conducted. These studies revealed that FlhF does not influence production of or signaling between the flagellar export apparatus and the FlgSR two-component regulatory system to activate σ54. Instead, our data suggest that FlhF functions in an independent pathway that converges with or works downstream of the flagellar export apparatus-FlgSR pathway to influence σ54-dependent gene expression. This study provides corroborative biochemical and genetic analyses suggesting that different activities of the C. jejuni FlhF GTPase are required for distinct steps in flagellar gene expression and biosynthesis. Our findings are likely applicable to many polarly flagellated bacteria that utilize FlhF in flagellar biosynthesis processes.

scholarly journals Rewiring of the Transcription Factor Network in Acute Myeloid Leukemia

2019 ◽  
Vol 18 ◽  
pp. 117693511985986 ◽  
Author(s):  
Salam A Assi ◽  
Constanze Bonifer ◽  
Peter N Cockerill
Keyword(s):  
Gene Expression ◽  
Acute Myeloid Leukemia ◽  
Transcription Factors ◽  
Myeloid Leukemia ◽  
Regulatory Networks ◽  
Regulatory Elements ◽  
Genes Encoding ◽  
Myeloid Development ◽  
Mitogen Activated Protein ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a highly heterogeneous cancer associated with different patterns of gene expression determined by the nature of their DNA mutations. These mutations mostly act to deregulate gene expression by various mechanisms at the level of the nucleus. By performing genome-wide epigenetic profiling of cis-regulatory elements, we found that AML encompasses different mutation-specific subclasses associated with the rewiring of the gene regulatory networks that drive differentiation into different directions away from normal myeloid development. By integrating epigenetic profiles with gene expression and chromatin conformation data, we defined pathways within gene regulation networks that were differentially rewired within each mutation-specific subclass of AML. This analysis revealed 2 major classes of AML: one class defined by mutations in signaling molecules that activate AP-1 via the mitogen-activated protein (MAP) kinase pathway and a second class defined by mutations within genes encoding transcription factors such as RUNX1/CBFβ and C/EBPα. By identifying specific DNA motifs protected from DNase I digestion at cis-regulatory elements, we were able to infer candidate transcription factors bound to these motifs. These integrated analyses allowed the identification of AML subtype-specific core regulatory networks that are required for AML development and maintenance, which could now be targeted in personalized therapies.

scholarly journals Analysis of a Growth-Phase-Regulated Two-Component Regulatory System in the Periodontal Pathogen Treponema denticola

2008 ◽  
Vol 190 (18) ◽  
pp. 6162-6169 ◽  
Author(s):  
Jesse R. Frederick ◽  
Elizabeth A. Rogers ◽  
Richard T. Marconi
Keyword(s):  
Growth Phase ◽  
Regulatory Networks ◽  
Response Regulator ◽  
Regulatory System ◽  
Open Reading Frames ◽  
Periodontal Pathogen ◽  
Treponema Denticola ◽  
Rt Pcr ◽  
Two Component ◽  
Transcriptional Regulatory Mechanisms

ABSTRACT Nothing is currently known regarding the global regulatory networks of Treponema denticola and other oral spirochetes. In this report, we assess the properties and potential phosphotransfer capability of a putative two-component regulatory system (TCS) of T. denticola that is formed by the products of open reading frames tde0032 (a sensor kinase) and tde0033 (a response regulator), henceforth designated AtcS and AtcR, respectively. Using PCR and DNA sequence analyses, atcS and atcR were demonstrated to be widely distributed and conserved among T. denticola isolates. Reverse transcription-PCR (RT-PCR) analyses revealed that these genes are cotranscribed and may also be expressed as part of a larger operon that includes several flanking genes. Analyses using 5′ rapid amplification of cDNA ends identified the transcriptional start sites for these operons and provided evidence that some of these genes may be independently transcribed from internal promoters. Real-time RT-PCR and Western blot analysis revealed significant upregulation of atcRS during late-stage growth, indicating growth-phase-dependent expression. Lastly, the phosphorelay capability of the AtcRS system was assessed and demonstrated using recombinant proteins. AtcS was found to undergo autophosphorylation and to transfer phosphate to AtcR. These analyses represent the first description of a functional TCS in an oral spirochetes and provide insight into the transcriptional regulatory mechanisms of these important bacteria.

scholarly journals Synthetic gene-regulatory networks in the opportunistic human pathogenStreptococcus pneumoniae

2020 ◽  
Vol 117 (44) ◽  
pp. 27608-27619 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Laurye Van Maele ◽  
Jean-Claude Sirard ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Virulence Factor ◽  
Gene Regulatory Networks ◽  
Regulatory Networks ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Synthetic Gene ◽  
Expression Control ◽  
Gene Expression Control ◽  
Gene Regulatory

Streptococcus pneumoniaecan cause disease in various human tissues and organs, including the ear, the brain, the blood, and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control inS. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND gates and IMPLY gates. We demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors. Indeed, we were able to rewire gene expression of the capsule operon, the main pneumococcal virulence factor, to be externally inducible (YES gate) or to act as an IMPLY gate (only expressed in absence of inducer). Importantly, we demonstrate that these synthetic gene-regulatory networks are functional in an influenza A virus superinfection murine model of pneumonia, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity ofS. pneumoniae.

scholarly journals Genetic Evidence for an Alternative Citrate-Dependent Biofilm Formation Pathway in Staphylococcus aureus That Is Dependent on Fibronectin Binding Proteins and the GraRS Two-Component Regulatory System

2008 ◽  
Vol 76 (6) ◽  
pp. 2469-2477 ◽  
Author(s):  
Robert M. Q. Shanks ◽  
Michael A. Meehl ◽  
Kimberly M. Brothers ◽  
Raquel M. Martinez ◽  
Niles P. Donegan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Binding Proteins ◽  
Regulatory System ◽  
Tca Cycle ◽  
Formation Pathway ◽  
Two Component ◽  
Fibronectin Binding ◽  
Tca Cycle Intermediates

ABSTRACT We reported previously that low concentrations of sodium citrate strongly promote biofilm formation by Staphylococcus aureus laboratory strains and clinical isolates. Here, we show that citrate promotes biofilm formation via stimulating both cell-to-surface and cell-to-cell interactions. Citrate-stimulated biofilm formation is independent of the ica locus, and in fact, citrate represses polysaccharide adhesin production. We show that fibronectin binding proteins FnbA and FnbB and the global regulator SarA, which positively regulates fnbA and fnbB gene expression, are required for citrate's positive effects on biofilm formation, and citrate also stimulates fnbA and fnbB gene expression. Biofilm formation is also stimulated by several other tricarboxylic acid (TCA) cycle intermediates in an FnbA-dependent fashion. While aconitase contributes to biofilm formation in the absence of TCA cycle intermediates, it is not required for biofilm stimulation by these compounds. Furthermore, the GraRS two-component regulator and the GraRS-regulated efflux pump VraFG, identified for their roles in intermediate vancomycin resistance, are required for citrate-stimulated cell-to-cell interactions, but the GraRS regulatory system does not impact the expression of the fnbA and fnbB genes. Our data suggest that distinct genetic factors are required for the early steps in citrate-stimulated biofilm formation. Given the role of FnbA/FnbB and SarA in virulence in vivo and the lack of a role for ica-mediated biofilm formation in S. aureus catheter models of infection, we propose that the citrate-stimulated biofilm formation pathway may represent a clinically relevant pathway for the formation of these bacterial communities on medical implants.

scholarly journals Expression of Uptake Hydrogenase and Molybdenum Nitrogenase in Rhodobacter capsulatus Is Coregulated by the RegB-RegA Two-Component Regulatory System

2000 ◽  
Vol 182 (10) ◽  
pp. 2831-2837 ◽  
Author(s):  
Sylvie Elsen ◽  
Wanda Dischert ◽  
Annette Colbeau ◽  
Carl E. Bauer
Keyword(s):  
Photosynthetic Bacteria ◽  
Rhodobacter Capsulatus ◽  
Regulatory System ◽  
Photosynthetic Bacterium ◽  
Uptake Hydrogenase ◽  
Carbon And Nitrogen ◽  
Cellular Energy ◽  
Purple Photosynthetic Bacteria ◽  
Two Component

ABSTRACT Purple photosynthetic bacteria are capable of generating cellular energy from several sources, including photosynthesis, respiration, and H2 oxidation. Under nutrient-limiting conditions, cellular energy can be used to assimilate carbon and nitrogen. This study provides the first evidence of a molecular link for the coregulation of nitrogenase and hydrogenase biosynthesis in an anoxygenic photosynthetic bacterium. We demonstrated that molybdenum nitrogenase biosynthesis is under the control of the RegB-RegA two-component regulatory system in Rhodobacter capsulatus. Footprint analyses and in vivo transcription studies showed that RegA indirectly activates nitrogenase synthesis by binding to and activating the expression of nifA2, which encodes one of the two functional copies of the nif-specific transcriptional activator, NifA. Expression of nifA2 but notnifA1 is reduced in the reg mutants up to eightfold under derepressing conditions and is also reduced under repressing conditions. Thus, although NtrC is absolutely required fornifA2 expression, RegA acts as a coactivator ofnifA2. We also demonstrated that in regmutants, [NiFe]hydrogenase synthesis and activity are increased up to sixfold. RegA binds to the promoter of the hydrogenase gene operon and therefore directly represses its expression. Thus, the RegB-RegA system controls such diverse processes as energy-generating photosynthesis and H2 oxidation, as well as the energy-demanding processes of N2 fixation and CO2 assimilation.

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