scholarly journals Role of the Global Transcriptional Regulator PrrA in Rhodobacter sphaeroides 2.4.1: Combined Transcriptome and Proteome Analysis

2008 ◽  
Vol 190 (14) ◽  
pp. 4831-4848 ◽  
Author(s):  
Jesus M. Eraso ◽  
Jung Hyeob Roh ◽  
Xiaohua Zeng ◽  
Stephen J. Callister ◽  
Mary S. Lipton ◽  
...  
Keyword(s):  
Rhodobacter Sphaeroides ◽  
Regulatory System ◽  
Proteome Analysis ◽  
Orthologous Group ◽  
Transcriptional Level ◽  
Chromatographic Study ◽  
Metabolic Genes ◽  
Genes Encoding ◽  
Parameter Values

ABSTRACTThe PrrBA two-component regulatory system is a major global regulator inRhodobacter sphaeroides2.4.1. Here we have compared the transcriptome and proteome profiles of the wild-type (WT) and mutant PrrA2 cells grown anaerobically in the dark with dimethyl sulfoxide as an electron acceptor. Approximately 25% of the genes present in the PrrA2 genome are regulated by PrrA at the transcriptional level, either directly or indirectly, by twofold or more relative to the WT. The genes affected are widespread throughout all COG (cluster of orthologous group) functional categories, with previously unsuspected “metabolic” genes affected in PrrA2 cells. PrrA was found to act as both an activator and a repressor of transcription, with more genes being repressed in the presence of PrrA (9:5 ratio). An analysis of the genes encoding the 1,536 peptides detected through our chromatographic study, which corresponds to 36% coverage of the genome, revealed that approximately 20% of the genes encoding these proteins were positively regulated, whereas approximately 32% were negatively regulated by PrrA, which is in excellent agreement with the percentages obtained for the whole-genome transcriptome profile. In addition, comparison of the transcriptome and proteome mean parameter values for WT and PrrA2 cells showed good qualitative agreement, indicating that transcript regulation paralleled the corresponding protein abundance, although not one for one. The microarray analysis was validated by direct mRNA measurement of randomly selected genes that were both positively and negatively regulated.lacZtranscriptional andkantranslational fusions enabled us to map putative PrrA binding sites and revealed potential gene targets for indirect regulation by PrrA.

scholarly journals Hierarchical Regulation of Photosynthesis Gene Expression by the Oxygen-Responsive PrrBA and AppA-PpsR Systems of Rhodobacter sphaeroides

2008 ◽  
Vol 190 (24) ◽  
pp. 8106-8114 ◽  
Author(s):  
Larissa Gomelsky ◽  
Oleg V. Moskvin ◽  
Rachel A. Stenzel ◽  
Denise F. Jones ◽  
Timothy J. Donohue ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rhodobacter Sphaeroides ◽  
Response Regulator ◽  
Photosynthetic Apparatus ◽  
Regulatory System ◽  
Structural Proteins ◽  
Gene Encoding ◽  
Genes Encoding ◽  
Photosynthetic Complexes ◽  
Photosynthesis Gene

ABSTRACT In the facultatively phototrophic proteobacterium Rhodobacter sphaeroides, formation of the photosynthetic apparatus is oxygen dependent. When oxygen tension decreases, the response regulator PrrA of the global two-component PrrBA system is believed to directly activate transcription of the puf, puh, and puc operons, encoding structural proteins of the photosynthetic complexes, and to indirectly upregulate the photopigment biosynthesis genes bch and crt. Decreased oxygen also results in inactivation of the photosynthesis-specific repressor PpsR, bringing about derepression of the puc, bch, and crt operons. We uncovered a hierarchical relationship between these two regulatory systems, earlier thought to function independently. We also more accurately assessed the spectrum of gene targets of the PrrBA system. First, expression of the appA gene, encoding the PpsR antirepressor, is PrrA dependent, which establishes one level of hierarchical dominance of the PrrBA system over AppA-PpsR. Second, restoration of the appA transcript to the wild-type level is insufficient for rescuing phototrophic growth impairment of the prrA mutant, whereas inactivation of ppsR is sufficient. This suggests that in addition to controlling appA transcription, PrrA affects the activity of the AppA-PpsR system via an as yet unidentified mechanism(s). Third, PrrA directly activates several bch and crt genes, traditionally considered to be the PpsR targets. Therefore, in R. sphaeroides, the global PrrBA system regulates photosynthesis gene expression (i) by rigorous control over the photosynthesis-specific AppA-PpsR regulatory system and (ii) by extensive direct transcription activation of genes encoding structural proteins of photosynthetic complexes as well as genes encoding photopigment biosynthesis enzymes.

scholarly journals Assembly of Fimbrial Structures in Pseudomonas aeruginosa: Functionality and Specificity of Chaperone-Usher Machineries

2007 ◽  
Vol 189 (9) ◽  
pp. 3547-3555 ◽  
Author(s):  
Ségolène Ruer ◽  
Silke Stender ◽  
Alain Filloux ◽  
Sophie de Bentzmann
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Regulatory System ◽  
Gene Clusters ◽  
Solid Surfaces ◽  
Standard Laboratory ◽  
Assembly Mechanism ◽  
Genes Encoding ◽  
High Level

ABSTRACT Fimbrial or nonfimbrial adhesins assembled by the bacterial chaperone-usher pathway have been demonstrated to play a key role in pathogenesis. Such an assembly mechanism has been exemplified in uropathogenic Escherichia coli strains with the Pap and the Fim systems. In Pseudomonas aeruginosa, three gene clusters (cupA, cupB, and cupC) encoding chaperone-usher pathway components have been identified in the genome sequence of the PAO1 strain. The Cup systems differ from the Pap or Fim systems, since they obviously lack numbers of genes encoding fimbrial subunits. Nevertheless, the CupA system has been demonstrated to be involved in biofilm formation on solid surfaces, whereas the role of the CupB and CupC systems in biofilm formation could not be clearly elucidated. Moreover, these gene clusters were described as poorly expressed under standard laboratory conditions. The cupB and cupC clusters are directly under the control of a two-component regulatory system designated RocA1/S1/R. In this study, we revealed that Roc1-dependent induction of the cupB and cupC genes resulted in a high level of biofilm formation, with CupB and CupC acting with synergy in clustering bacteria for microcolony formation. Very importantly, this phenotype was associated with the assembly of cell surface fimbriae visualized by electron microscopy. Finally, we observed that the CupB and CupC systems are specialized in the assembly of their own fimbrial subunits and are not exchangeable.

scholarly journals A Two-Component covRS Regulatory System Regulates Expression of Fructosyltransferase and a Novel Extracellular Carbohydrate in Streptococcus mutans

2004 ◽  
Vol 72 (7) ◽  
pp. 3968-3973 ◽  
Author(s):  
Song F. Lee ◽  
Gillian D. Delaney ◽  
Mohammad Elkhateeb
Keyword(s):  
Streptococcus Mutans ◽  
Glucuronic Acid ◽  
Regulatory System ◽  
Transcriptional Level ◽  
Wild Type ◽  
Reverse Transcription Pcr ◽  
Defective Mutant ◽  
Two Component ◽  
Cariogenic Bacterium

ABSTRACT The expression of fructosyltransferase (FTF), the enzyme that synthesizes fructan from sucrose, is regulated in the cariogenic bacterium Streptococcus mutans. However, the exact mechanism of FTF regulation is unknown. In this study, the role of a two-component regulatory system (covRS) in FTF expression was investigated. A CovR-defective mutant of S. mutans NG8 was constructed by homologous recombination. By use of immunoblotting, the mutant was shown to overexpress FTF in the absence of sucrose, while the wild type and a covRS-complemented mutant showed sucrose-inducible FTF expression. Reverse transcription-PCR showed that the ftf transcript levels were increased in the covR mutant, suggesting regulation at the transcriptional level. The covR mutant was also found to overproduce extracellular carbohydrate, and this phenotype was reversed by covRS complementation. Paper chromatographic studies and chemical tests showed that the extracellular carbohydrate contained glucose and glucuronic acid but not fructose. These results suggest that the extracellular carbohydrate was not fructan. The production of a glucose- and glucuronic acid-containing extracellular carbohydrate has not been reported for S. mutans and may be considered novel. In conclusion, the results indicate that the expression of FTF and a glucose- and glucuronic acid-containing carbohydrate was negatively regulated by the covRS two-component regulatory system in S. mutans.

scholarly journals Role of MicroRNAs in the Development and Progression of the Four Medulloblastoma Subgroups

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6323
Author(s):  
Emilia Bevacqua ◽  
Jasmin Farshchi ◽  
Maria Victoria Niklison-Chirou ◽  
Paola Tucci
Keyword(s):  
Sonic Hedgehog ◽  
Regulatory System ◽  
Transcriptional Level ◽  
Cell Of Origin ◽  
Cellular Functions ◽  
Group 4 ◽  
A Genome ◽  
The Central Nervous System ◽  
Group 3

Medulloblastoma is the most frequent malignant brain tumour in children. Medulloblastoma originate during the embryonic stage. They are located in the cerebellum, which is the area of the central nervous system (CNS) responsible for controlling equilibrium and coordination of movements. In 2012, medulloblastoma were divided into four subgroups based on a genome-wide analysis of RNA expression. These subgroups are named Wingless, Sonic Hedgehog, Group 3 and Group 4. Each subgroup has a different cell of origin, prognosis, and response to therapies. Wingless and Sonic Hedgehog medulloblastoma are so named based on the main mutation originating these tumours. Group 3 and Group 4 have generic names because we do not know the key mutation driving these tumours. Gene expression at the post-transcriptional level is regulated by a group of small single-stranded non-coding RNAs. These microRNA (miRNAs or miRs) play a central role in several cellular functions such as cell differentiation and, therefore, any malfunction in this regulatory system leads to a variety of disorders such as cancer. The role of miRNAs in medulloblastoma is still a topic of intense clinical research; previous studies have mostly concentrated on the clinical entity of the single disease rather than in the four molecular subgroups. In this review, we summarize the latest discoveries on miRNAs in the four medulloblastoma subgroups.

scholarly journals MicroRNA AND TUBERCULOSIS

2018 ◽  
Vol 8 (3) ◽  
pp. 309-315
Author(s):  
V. V. Eremeev ◽  
V. V. Evstifeev ◽  
G. S. Shepelkova ◽  
A. E. Ergeshova ◽  
M. A. Bagirov
Keyword(s):  
Drug Resistance ◽  
Multiple Drug Resistance ◽  
Fine Tuning ◽  
Tuberculosis Infection ◽  
Multiple Drug ◽  
Transcriptional Level ◽  
Genes Encoding ◽  
Mdr Tb ◽  
Inflammatory Processes

In 2015, more than 10% of tuberculosis (TB)-related deaths were attributable to M. tuberculosis with multiple drug-resistance (MDR-TB) and extensively drug-resistance (XDR-TB) (WHO 2016). In combination with insufficient commitment to the treatment regimen, the genetic heterogeneity and clonality of the patient's M. tuberculosis, as well as the poor permeability of the tuberculosis granuloma for the drug, can lead to monotherapy, despite the use of several drugs, which further promotes the spread of MDR and XDR-TB. Of particular concern is the rapid spread of resistance to newly introduced into clinical practice second-line drugs, intended for the treatment of MDR-TB — delamanid and bedaquiline. Thus, the spread of drug resistance to chemotherapy, along with the limited possibilities of chemotherapy in patients with MDR-TB and XDR-TB, dictate the need to supplement canonical chemotherapy with TB treatment methods directed at the host. MicroRNAs (miRs) are short sequences of single-stranded RNA that control up to 60% of genes encoding protein synthesis at a post-transcriptional level. Accumulating data points to the essential role of miRs in fine tuning the host response to infection, primarily by modulating the expression of proteins involved in the reactions of innate and adaptive immune responses. Despite the fact that the established functions of miRs activity are intracellular, a number of studies have discovered highly stable extracellular miRs circulating in blood. Currently, the possibility of using these molecules as biomarkers is being actively investigated. Chronic TB inflammation is characterized by parallel or step-bystep development of regulatory and pro-inflammatory processes that affect the severity and outcome of the disease. Both pro- and anti-inflammatory effects are elements of the bacterial strategy in the struggle for survival in the host organism. In this review we discuss the role of miRs as markers of tuberculosis infection, the nature and prognosis of the course of the disease, the involvement of miRs in the regulation of the innate and adaptive immunity in tuberculosis infection, and the perspectives for clinical usage of miRs as means for diagnosis and treatment of tuberculosis.

scholarly journals Genome-scale reconstruction of Gcn4/ATF4 networks driving a growth program

PLoS Genetics ◽  
2020 ◽  
Vol 16 (12) ◽  
pp. e1009252
Author(s):  
Rajalakshmi Srinivasan ◽  
Adhish S. Walvekar ◽  
Zeenat Rashida ◽  
Aswin Seshasayee ◽  
Sunil Laxman
Keyword(s):  
Amino Acid ◽  
Promoter Regions ◽  
Nucleotide Biosynthesis ◽  
Translation Machinery ◽  
Metabolic Genes ◽  
Genome Wide ◽  
Genes Encoding ◽  
Genome Scale ◽  
Global Growth

Growth and starvation are considered opposite ends of a spectrum. To sustain growth, cells use coordinated gene expression programs and manage biomolecule supply in order to match the demands of metabolism and translation. Global growth programs complement increased ribosomal biogenesis with sufficient carbon metabolism, amino acid and nucleotide biosynthesis. How these resources are collectively managed is a fundamental question. The role of the Gcn4/ATF4 transcription factor has been best studied in contexts where cells encounter amino acid starvation. However, high Gcn4 activity has been observed in contexts of rapid cell proliferation, and the roles of Gcn4 in such growth contexts are unclear. Here, using a methionine-induced growth program in yeast, we show that Gcn4/ATF4 is the fulcrum that maintains metabolic supply in order to sustain translation outputs. By integrating matched transcriptome and ChIP-Seq analysis, we decipher genome-wide direct and indirect roles for Gcn4 in this growth program. Genes that enable metabolic precursor biosynthesis indispensably require Gcn4; contrastingly ribosomal genes are partly repressed by Gcn4. Gcn4 directly binds promoter-regions and transcribes a subset of metabolic genes, particularly driving lysine and arginine biosynthesis. Gcn4 also globally represses lysine and arginine enriched transcripts, which include genes encoding the translation machinery. The Gcn4 dependent lysine and arginine supply thereby maintains the synthesis of the translation machinery. This is required to maintain translation capacity. Gcn4 consequently enables metabolic-precursor supply to bolster protein synthesis, and drive a growth program. Thus, we illustrate how growth and starvation outcomes are both controlled using the same Gcn4 transcriptional outputs that function in distinct contexts.

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.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

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