scholarly journals The INO80 Complex Requires the Arp5-Ies6 Subcomplex for Chromatin Remodeling and Metabolic Regulation

2016 ◽  
Vol 36 (6) ◽  
pp. 979-991 ◽  
Author(s):  
Wei Yao ◽  
Devin A. King ◽  
Sean L. Beckwith ◽  
Graeme J. Gowans ◽  
Kuangyu Yen ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Metabolic Regulation ◽  
Chromatin Remodeler ◽  
Transcriptional Responses ◽  
Mitochondrial Potential ◽  
Content Type ◽  
Expression Of Genes ◽  
Genomic Studies

ATP-dependent chromatin remodeling complexes are essential for transcription regulation, and yet it is unclear how these multisubunit complexes coordinate their activities to facilitate diverse transcriptional responses. In this study, we found that the conserved Arp5 and Ies6 subunits of theSaccharomyces cerevisiaeINO80 chromatin-remodeler form an abundant and distinct subcomplexin vivoand stimulate INO80-mediated activityin vitro. Moreover, our genomic studies reveal that the relative occupancy of Arp5-Ies6 correlates with nucleosome positioning at transcriptional start sites and expression levels of >1,000 INO80-regulated genes. Notably, these genes are significantly enriched in energy metabolism pathways. Specifically,arp5Δ,ies6Δ, andino80Δ mutants demonstrate decreased expression of genes involved in glycolysis and increased expression of genes in the oxidative phosphorylation pathway. Deregulation of these metabolic pathways results in constitutively elevated mitochondrial potential and oxygen consumption. Our results illustrate the dynamic nature of the INO80 complex assembly and demonstrate for the first time that a chromatin remodeler regulates glycolytic and respiratory capacity, thereby maintaining metabolic stability.

scholarly journals Mutations of the Listeria monocytogenes PeptidoglycanN-Deacetylase andO-Acetylase Result in Enhanced Lysozyme Sensitivity, Bacteriolysis, and Hyperinduction of Innate Immune Pathways

2011 ◽  
Vol 79 (9) ◽  
pp. 3596-3606 ◽  
Author(s):  
Chris S. Rae ◽  
Aimee Geissler ◽  
Paul C. Adamson ◽  
Daniel A. Portnoy
Keyword(s):  
Listeria Monocytogenes ◽  
Transcriptional Responses ◽  
Gram Positive ◽  
Content Type ◽  
Growth Defects ◽  
Gram Positive Bacteria ◽  
Host Cell Death

ABSTRACTListeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd−, Oat−, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd−and Pgd−Oat−double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM−macrophages. The addition of extracellular lysozyme to LysM−macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

scholarly journals Transcriptional Regulator LsrB of Sinorhizobium meliloti Positively Regulates the Expression of Genes Involved in Lipopolysaccharide Biosynthesis

2014 ◽  
Vol 80 (17) ◽  
pp. 5265-5273 ◽  
Author(s):  
Guirong Tang ◽  
Ying Wang ◽  
Li Luo
Keyword(s):  
Sinorhizobium Meliloti ◽  
Sodium Dodecyl ◽  
Host Cells ◽  
Content Type ◽  
Expression Of Genes ◽  
New Findings ◽  
Promoter Dna ◽  
Transcriptional Start Sites

ABSTRACTRhizobia induce nitrogen-fixing nodules on host legumes, which is important in agriculture and ecology. Lipopolysaccharide (LPS) produced by rhizobia is required for infection or bacteroid survival in host cells. Genes required for LPS biosynthesis have been identified in severalRhizobiumspecies. However, the regulation of their expression is not well understood. Here,Sinorhizobium melilotiLsrB, a member of the LysR family of transcriptional regulators, was found to be involved in LPS biosynthesis by positively regulating the expression of thelrp3-lpsCDEoperon. AnlsrBin-frame deletion mutant displayed growth deficiency, sensitivity to the detergent sodium dodecyl sulfate, and acidic pH compared to the parent strain. This mutant produced slightly less LPS due to lower expression of thelrp3operon. Analysis of the transcriptional start sites of thelrp3andlpsCDEgene suggested that they constitute one operon. The expression oflsrBwas positively autoregulated. The promoter region oflrp3was specifically precipitated by anti-LsrB antibodiesin vivo. The promoter DNA fragment containing TN11A motifs was bound by the purified LsrB proteinin vitro. These new findings suggest thatS. melilotiLsrB is associated with LPS biosynthesis, which is required for symbiotic nitrogen fixation on some ecotypes of alfalfa plants.

scholarly journals Smarca5 mediated epigenetic programming facilitates fetal HSPC development in vertebrates

Blood ◽  
2020 ◽  
Author(s):  
Yanyan Ding ◽  
Wen Wang ◽  
Dongyuan Ma ◽  
Guixian Liang ◽  
Zhixin Kang ◽  
...  
Keyword(s):  
Chromatin Remodeling ◽  
Chromatin Accessibility ◽  
Rna Seq ◽  
Chromatin Remodeler ◽  
Dynamic Changes ◽  
Functional Assays ◽  
Epigenetic Programming

Nascent HSPCs acquire definitive hematopoietic characteristics only when they develop into fetal HSPCs; however, the mechanisms underlying fetal HSPC development are poorly understood. Here, we profiled the chromatin accessibility and transcriptional features of zebrafish nascent- and fetal HSPCs using ATAC-seq and RNA-seq and revealed dynamic changes during HSPC transition. Functional assays demonstrated that chromatin remodeler-mediated epigenetic programming facilitates fetal HSPC development in vertebrates. Systematical screening of chromatin remodeler-related genes identified that smarca5 is responsible for the maintenance of chromatin accessibility at promoters of hematopoiesis-related genes in fetal HSPCs. Mechanistically, Smarca5 interacts with Nucleolin to promote chromatin remodeling, thereby facilitating genomic binding of transcription factors to regulate expression of hematopoietic regulators such as bcl11ab. Our results unravel a new role of epigenetic regulation and reveal that Smarca5-mediated epigenetic programming is responsible for fetal HSPC development, which will provide new insights into the generation of functional HSPCs both in vivo and in vitro.

scholarly journals Anopheles gambiaeLackingAgTRIOInefficiently TransmitsPlasmodium bergheito Mice

2019 ◽  
Vol 87 (9) ◽  
Author(s):  
Yu-Min Chuang ◽  
Marianna Freudzon ◽  
Jing Yang ◽  
Yuemei Dong ◽  
George Dimopoulos ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Local Environment ◽  
Salivary Protein ◽  
Content Type ◽  
Relative Contribution ◽  
Expression Of Genes ◽  
Tnf Α ◽  
Sporozoite Infection

ABSTRACTAntibodies to AgTRIO, a mosquito salivary protein, partially reduce the initialPlasmodiumburden in mice. We therefore silencedAgTRIOin mosquitoes and determined the relative contribution of AgTRIO to the ability ofAnopheles gambiaeto transmitPlasmodium bergheito mice. RNA interference-mediated silencing ofAgTRIO inA. gambiaeresulted in a 60% reduction inAgTRIOexpression. The decrease inAgTRIOexpression did not alter the burden ofPlasmodiumsporozoites in mosquito salivary glands. When experimentally injected into mice, sporozoites fromAgTRIO-silenced mosquitoes colonized the liver less effectively than sporozoites from control mosquitoes. Silencing ofAgTRIOdid not decrease the infectivity of sporozoitesin vitroor influence the expression of genes associated withPlasmodiumcell adhesion or traversal activity. AgTRIO decreased the expression of proinflammation cytokines by splenocytesin vitro. Moreover,in vivo, AgTRIO decreased the expression ofTNF-αwhen coinjected with sporozoites into the skin and there was moreTNF-αexpression at the bite site ofAgTRIOknockdown mosquitoes than at the bite site of control mosquitoes. AgTRIO therefore influences the local environment in the vertebrate host, which facilitatesPlasmodiumsporozoite infection in mice.

scholarly journals Bacterial Subfamily of LuxR Regulators That Respond to Plant Compounds

2011 ◽  
Vol 77 (13) ◽  
pp. 4579-4588 ◽  
Author(s):  
Sujatha Subramoni ◽  
Juan F. Gonzalez ◽  
Aaron Johnson ◽  
Maria Péchy-Tarr ◽  
Laurène Rochat ◽  
...  
Keyword(s):  
Plant Pathogens ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Promoter ◽  
Pythium Ultimum ◽  
Content Type ◽  
Expression Of Genes ◽  
Plant Compounds

ABSTRACTPseudomonas fluorescensare rhizobacteria known for their biocontrol properties. Several antimicrobial functions are crucial for this process, and the experiments described here investigate the modulation of their expression during the plant-bacterium interaction. The role of a LuxR family regulator in interkingdom signaling has been investigated using genome-scale transcriptome analysis, gene promoter studiesin vivoandin vitro, biocontrol assays, and response to plant compounds. PsoR, a LuxR solo or orphan regulator ofP. fluorescens, was identified. PsoR is solubilized and activates alux-box-containing promoter only in the presence of macerated plants, suggesting the presence of a plant molecule(s) that most likely binds to PsoR. Gene expression profiles revealed that genes involved in the inhibition of plant pathogens were affected by PsoR, including a chitinase gene, iron metabolism genes, and biosynthetic genes of antifungal compounds. 2,4-Diacetylphloroglucinol production is PsoR dependent bothin vitroandin vivo.psoRmutants were significantly reduced for their ability to protect wheat plants from root rot, and damping-off caused byPythium ultimuminfection. PsoR most likely senses a molecule(s) in the plant and modulates expression of genes that have a role in biocontrol. PsoR and related proteins form a subfamily of LuxR family regulators in plant-associated bacteria.

scholarly journals RNA Sequencing Reveals Differences between the Global Transcriptomes of Salmonella enterica Serovar Enteritidis Strains with High and Low Pathogenicities

2013 ◽  
Vol 80 (3) ◽  
pp. 896-906 ◽  
Author(s):  
Devendra H. Shah
Keyword(s):  
Rna Sequencing ◽  
Salmonella Enterica ◽  
Negative Binomial ◽  
Phenotypic Diversity ◽  
Functional Characterization ◽  
Salmonella Enterica Serovar Enteritidis ◽  
Content Type ◽  
Expression Of Genes

ABSTRACTSalmonella entericaserovar Enteritidis is one of the important causes of bacterial food-borne gastroenteritis worldwide. Field strains ofS. Enteritidis are relatively genetically homogeneous; however, they show extensive phenotypic diversity and differences in virulence potential. RNA sequencing (RNA-Seq) was used to characterize differences in the global transcriptome between several genetically similar but phenotypically diverse poultry-associated field strains ofS. Enteritidis grown in laboratory medium at avian body temperature (42°C). TheseS. Enteritidis strains were previously characterized as high-pathogenicity (HP;n= 3) and low-pathogenicity (LP;n= 3) strains based on bothin vitroandin vivovirulence assays. Using the negative binomial distribution-based statistical tools edgeR and DESeq, 252 genes were identified as differentially expressed in LP strains compared with their expression in the HP strains (P< 0.05). A majority of genes (235, or 93.2%) showed significantly reduced expression, whereas a few genes (17, or 6.8%) showed increased expression in all LP strains compared with HP strains. LP strains showed a unique transcriptional profile that is characterized by significantly reduced expression of several transcriptional regulators and reduced expression of genes involved in virulence (e.g.,Salmonellapathogenicity island 1 [SPI-1], SPI-5, and fimbrial and motility genes) and protection against osmotic, oxidative, and other stresses, such as iron-limiting conditions commonly encountered within the host. Several functionally uncharacterized genes also showed reduced expression. This study provides a first concise view of the global transcriptional differences between field strains ofS. Enteritidis with various levels of pathogenicity, providing the basis for future functional characterization of several genes with potential roles in virulence or stress regulation ofS. Enteritidis.

scholarly journals Bacterial Nucleoid-Associated Protein Uncouples Transcription Levels from Transcription Timing

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Igor Zwir ◽  
Won-Sik Yeo ◽  
Dongwoo Shin ◽  
Tammy Latifi ◽  
Henry Huang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Genes ◽  
Transcriptional Regulator ◽  
Mrna Levels ◽  
Content Type ◽  
Expression Of Genes ◽  
Serovar Typhimurium ◽  
Expression Behavior

ABSTRACTThe histone-like nucleoid-structuring (H-NS) protein binds to horizontally acquired genes in the bacteriumSalmonella entericaserovar Typhimurium, silencing their expression. We now report that overcoming the silencing effects of H-NS imposes a delay in the expression of genes activated by the transcriptional regulator PhoP. We determine that PhoP-activated genes ancestral toSalmonellaare expressed before those acquired horizontally. This expression timing reflects thein vivooccupancy of the corresponding promoters by the PhoP protein. These results are surprising because some of these horizontally acquired genes reached higher mRNA levels than ancestral genes expressed earlier and were transcribed from promoters harboring PhoP-binding sites with higherin vitroaffinity for the PhoP protein. Our findings challenge the often-made assumption that for genes coregulated by a given transcription factor, early genes are transcribed to higher mRNA levels than those transcribed at later times. Moreover, they provide a singular example of how gene ancestry can impact expression timing.IMPORTANCEWe report that gene ancestry dictates the expression behavior of genes under the direct control of theSalmonellatranscriptional regulator PhoP. That is, ancestral genes are transcribed before horizontally acquired genes. This reflects both the need to overcome silencing by the H-NS protein of the latter genes and the architecture of the corresponding promoters. Unexpectedly, transcription levels do not reflect transcription timing. Our results illustrate how a bacterium can exhibit an elaborate temporal expression behavior among genes coregulated by a transcription factor even though the products encoded by the target genes do not participate in a morphological or developmental pathway.

scholarly journals Arsenite Oxidase Also Functions as an Antimonite Oxidase

2015 ◽  
Vol 81 (6) ◽  
pp. 1959-1965 ◽  
Author(s):  
Qian Wang ◽  
Thomas P. Warelow ◽  
Yoon-Suk Kang ◽  
Christine Romano ◽  
Thomas H. Osborne ◽  
...  
Keyword(s):  
Environmental Protection Agency ◽  
Large Subunit ◽  
Environmental Pollutants ◽  
Transcriptional Responses ◽  
Oxidation Activity ◽  
Content Type ◽  
Genes Encoding ◽  
Basic Features

ABSTRACTArsenic and antimony are toxic metalloids and are considered priority environmental pollutants by the U.S. Environmental Protection Agency. Significant advances have been made in understanding microbe-arsenic interactions and how they influence arsenic redox speciation in the environment. However, even the most basic features of how and why a microorganism detects and reacts to antimony remain poorly understood. Previous work withAgrobacterium tumefaciensstrain 5A concluded that oxidation of antimonite [Sb(III)] and arsenite [As(III)] required different biochemical pathways. Here, we show within vivoexperiments that a mutation inaioA[encoding the large subunit of As(III) oxidase] reduces the ability to oxidize Sb(III) by approximately one-third relative to the ability of the wild type. Further,in vitrostudies with the purified As(III) oxidase fromRhizobiumsp. strain NT-26 (AioA shares 94% amino acid sequence identity with AioA ofA. tumefaciens) provide direct evidence of Sb(III) oxidation but also show a significantly decreasedVmaxcompared to that of As(III) oxidation. TheaioBAgenes encoding As(III) oxidase are induced by As(III) but not by Sb(III), whereasarsRgene expression is induced by both As(III) and Sb(III), suggesting that detection and transcriptional responses for As(III) and Sb(III) differ. While Sb(III) and As(III) are similar with respect to cellular extrusion (ArsB or Acr3) and interaction with ArsR, they differ in the regulatory mechanisms that control the expression of genes encoding the different Ars or Aio activities. In summary, this study documents an enzymatic basis for microbial Sb(III) oxidation, although additional Sb(III) oxidation activity also is apparent in this bacterium.

scholarly journals Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jennifer K. Dowling ◽  
Remsha Afzal ◽  
Linden J. Gearing ◽  
Mariana P. Cervantes-Silva ◽  
Stephanie Annett ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Mitochondrial Dynamics ◽  
Interleukin 10 ◽  
Metabolic Reprogramming ◽  
In Vivo Model ◽  
Macrophage Polarisation ◽  
Inflammatory Status ◽  
Inflammatory Macrophages

AbstractMitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2−/− mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell.

scholarly journals In vivo transcriptome analysis provides insights into host-dependent expression of virulence factors by Yersinia entomophaga MH96, during infection of Galleria mellonella

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Amber R Paulson ◽  
Maureen O’Callaghan ◽  
Xue-Xian Zhang ◽  
Paul B Rainey ◽  
Mark R H Hurst
Keyword(s):  
Galleria Mellonella ◽  
Functional Enrichment ◽  
Natural Environments ◽  
Insecticidal Toxin ◽  
Heat Stable ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Cell Densities

Abstract The function of microbes can be inferred from knowledge of genes specifically expressed in natural environments. Here, we report the in vivo transcriptome of the entomopathogenic bacterium Yersinia entomophaga MH96, captured during initial, septicemic, and pre-cadaveric stages of intrahemocoelic infection in Galleria mellonella. A total of 1285 genes were significantly upregulated by MH96 during infection; 829 genes responded to in vivo conditions during at least one stage of infection, 289 responded during two stages of infection, and 167 transcripts responded throughout all three stages of infection compared to in vitro conditions at equivalent cell densities. Genes upregulated during the earliest infection stage included components of the insecticidal toxin complex Yen-TC (chi1, chi2, and yenC1), genes for rearrangement hotspot element containing protein yenC3, cytolethal distending toxin cdtAB, and vegetative insecticidal toxin vip2. Genes more highly expressed throughout the infection cycle included the putative heat-stable enterotoxin yenT and three adhesins (usher-chaperone fimbria, filamentous hemagglutinin, and an AidA-like secreted adhesin). Clustering and functional enrichment of gene expression data also revealed expression of genes encoding type III and VI secretion system-associated effectors. Together these data provide insight into the pathobiology of MH96 and serve as an important resource supporting efforts to identify novel insecticidal agents.

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