Factor XIII-A is involved in the regulation of gene expression in alternatively activated human macrophages

2010 ◽  
Vol 104 (10) ◽  
pp. 709-717 ◽  
Author(s):  
Dániel Töröcsik ◽  
Lajos Széles ◽  
György Paragh ◽  
Zsuzsa Rákosy ◽  
Helga Bárdos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Factor Xiii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Wound Response ◽  
Interleukin 4 ◽  
Alternative Activation ◽  
Wild Type ◽  
Functional Clustering ◽  
Alternatively Activated

SummaryFactor XIII subunit A (FXIII-A) is one of the most overrepresented genes that is expressed during the alternative activation of macrophages. Based on its substrate profile and its cellular localisation, FXIII-A is thought to function as an intracellular/intranuclear transglutaminase. Our aim was to find role for the intracellular FXIII-A by comparing the microarray profiles of alternatively activated monocyte-derived macrophages. Microarray analyses of FXIII-A-deficient patients and healthy controls were evaluated, followed by functional clustering of the differentially expressed genes. After a 48-hour differentiation in the presence of interleukin 4 (IL4), 1,017 probes out of the 24,398 expressed in macrophages from FXIII-A- deficient samples were IL4 sensitive, while only 596 probes were IL4 sensitive in wild-type samples. Of these genes, 307 were induced in both the deficient and the wild-type macrophages. Our results revealed that FXIII-A has important role(s) in mediating gene expression changes in macrophages during alternative activation. Functional clustering of the target genes carried out using Cytoscape/BiNGO and Ingenuity Pathways Analysis programs showed that, in the absence of FXIII-A, the most prominent differences are related to immune functions and to wound response. Our findings suggest that functional impairment of macrophages at the level of gene expression regulation plays a role in the wound healing defects of FXIII-A-deficient patients.

scholarly journals The nucleoplasmic interactions among Lamin A/C-pRB-LAP2α-E2F1 are modulated by dexamethasone

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anastasia Ricci ◽  
Sara Orazi ◽  
Federica Biancucci ◽  
Mauro Magnani ◽  
Michele Menotta
Keyword(s):  
Gene Expression ◽  
Cell Cycle Progression ◽  
Regulation Of Gene Expression ◽  
Lamin A ◽  
Wild Type ◽  
Cycle Progression ◽  
C Dynamics ◽  
E2f Transcription Factor ◽  
Transcription Factor 1

AbstractAtaxia telangiectasia (AT) is a rare genetic neurodegenerative disease. To date, there is no available cure for the illness, but the use of glucocorticoids has been shown to alleviate the neurological symptoms associated with AT. While studying the effects of dexamethasone (dex) in AT fibroblasts, by chance we observed that the nucleoplasmic Lamin A/C was affected by the drug. In addition to the structural roles of A-type lamins, Lamin A/C has been shown to play a role in the regulation of gene expression and cell cycle progression, and alterations in the LMNA gene is cause of human diseases called laminopathies. Dex was found to improve the nucleoplasmic accumulation of soluble Lamin A/C and was capable of managing the large chromatin Lamin A/C scaffolds contained complex, thus regulating epigenetics in treated cells. In addition, dex modified the interactions of Lamin A/C with its direct partners lamin associated polypeptide (LAP) 2a, Retinoblastoma 1 (pRB) and E2F Transcription Factor 1 (E2F1), regulating local gene expression dependent on E2F1. These effects were differentially observed in both AT and wild type (WT) cells. To our knowledge, this is the first reported evidence of the role of dex in Lamin A/C dynamics in AT cells, and may represent a new area of research regarding the effects of glucocorticoids on AT. Moreover, future investigations could also be extended to healthy subjects or to other pathologies such as laminopathies since glucocorticoids may have other important effects in these contexts as well.

RNA Modifications in the Central Nervous System

2020 ◽  
Author(s):  
Dan Ohtan Wang
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Gene Expression Regulation ◽  
Spinal Injury ◽  
Regulation Of Gene Expression ◽  
Modified Nucleosides ◽  
Rna Modifications ◽  
The Central Nervous System ◽  
Post Transcriptional Regulation ◽  
The Brain

Epitranscriptomics, a recently emerged field to investigate post-transcriptional regulation of gene expression through enzyme-mediated RNA modifications, is rapidly evolving and integrating with neuroscience. Using a rich repertoire of modified nucleosides and strategically positioning them to the functionally important and evolutionarily conserved regions of the RNA, epitranscriptomics dictates RNA-mediated cell function. The new field is quickly changing our view of the genetic geography in the brain during development and plasticity, impacting major functions from cortical neurogenesis, circadian rhythm, learning and memory, to reward, addiction, stress, stroke, and spinal injury, etc. Thus understanding the molecular components and operational rules of this pathway is becoming a key for us to decipher the genetic code for brain development, function, and disease. What RNA modifications are expressed in the brain? What RNAs carry them and rely on them for function? Are they dynamically regulated? How are they regulated and how do they contribute to gene expression regulation and brain function? This chapter summarizes recent advances that are beginning to answer these questions.

scholarly journals Roles of Transposable Elements in the Different Layers of Gene Expression Regulation

2019 ◽  
Vol 20 (22) ◽  
pp. 5755 ◽  
Author(s):  
Denise Drongitis ◽  
Francesco Aniello ◽  
Laura Fucci ◽  
Aldo Donizetti
Keyword(s):  
Gene Expression ◽  
Transposable Elements ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Chromatin Modification ◽  
Essential Element ◽  
Protein Translation ◽  
Expression Regulation ◽  
Molecular Processes ◽  
Eukaryotic Genomes

The biology of transposable elements (TEs) is a fascinating and complex field of investigation. TEs represent a substantial fraction of many eukaryotic genomes and can influence many aspects of DNA function that range from the evolution of genetic information to duplication, stability, and gene expression. Their ability to move inside the genome has been largely recognized as a double-edged sword, as both useful and deleterious effects can result. A fundamental role has been played by the evolution of the molecular processes needed to properly control the expression of TEs. Today, we are far removed from the original reductive vision of TEs as “junk DNA”, and are more convinced that TEs represent an essential element in the regulation of gene expression. In this review, we summarize some of the more recent findings, mainly in the animal kingdom, concerning the active roles that TEs play at every level of gene expression regulation, including chromatin modification, splicing, and protein translation.

scholarly journals Schistosoma mansoni Hemozoin Modulates Alternative Activation of Macrophages via Specific Suppression of Retnla Expression and Secretion

2012 ◽  
Vol 81 (1) ◽  
pp. 133-142 ◽  
Author(s):  
Martha Truscott ◽  
D. Andrew Evans ◽  
Matt Gunn ◽  
Karl F. Hoffmann
Keyword(s):  
Schistosoma Mansoni ◽  
Macrophage Activation ◽  
Inflammatory Responses ◽  
Interleukin 4 ◽  
Alternative Activation ◽  
Content Type ◽  
Hepatic Expression ◽  
Life Years ◽  
Alternatively Activated

The trematodeSchistosoma mansoniis one of the etiological agents of schistosomiasis, a key neglected tropical disease responsible for an estimated annual loss of 70 million disability-adjusted life years. Hematophagy represents the primary nutrient acquisition pathway of this parasite, but digestion of hemoglobin also liberates toxic heme. Schistosomes detoxify heme via crystallization into hemozoin, which is subsequently regurgitated into the host's circulation. Here we demonstrate that during experimental schistosomiasis, hemozoin accumulating in the mouse liver is taken up by phagocytes at a time coincident with the development of the egg-induced T-helper 2 (Th2) granulomatous immune response. Furthermore, the uptake of hemozoin also coincides with the hepatic expression of markers of alternative macrophage activation. Alternatively activated macrophages are a key effector cell population associated with protection against schistosomiasis, making hemozoin well placed to play an important immunomodulatory role in this disease. To systematically explore this hypothesis,S. mansonihemozoin was purified and added toin vitrobone marrow-derived macrophage cultures concurrently exposed to cytokines chosen to reflect the shifting state of macrophage activationin vivo. Macrophages undergoing interleukin-4 (IL-4)-induced alternative activation in the presence of hemozoin developed a phenotype specifically lacking inRetnla, a characteristic alternatively activated macrophage product associated with regulation of Th2 inflammatory responses. As such, in addition to its important detoxification role during hematophagy, we propose that schistosome hemozoin also provides a potent immunomodulatory function in the coevolved network of host-parasite relationships during schistosomiasis.

scholarly journals Using pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs

2018 ◽  
Author(s):  
Xiaofeng Xu ◽  
Haishuo Ji ◽  
Zhi Cheng ◽  
Xiufeng Jin ◽  
Xue Yao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Steady State ◽  
Small Rnas ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Cost Effective ◽  
Rna Degradation ◽  
Point Of View ◽  
Rna Seq ◽  
Dsrna Cleavage

AbstractIn this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5’ end and 3’ end small RNAs. 5’ and 3’ sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5’, 3’ and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5’, 3’ and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

scholarly journals From Intracellular Bacteria to Differentiated Bacteroids: Transcriptome and Metabolome Analysis inAeschynomeneNodules Using theBradyrhizobiumsp. Strain ORS285bclAMutant

2019 ◽  
Vol 201 (17) ◽  
Author(s):  
Florian Lamouche ◽  
Anaïs Chaumeret ◽  
Ibtissem Guefrachi ◽  
Quentin Barrière ◽  
Olivier Pierre ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcriptome Analysis ◽  
Soil Bacteria ◽  
Regulation Of Gene Expression ◽  
Nitrogen Fertilizers ◽  
Peptide Transporter ◽  
Intracellular Bacteria ◽  
Nitrogen Fixing ◽  
Wild Type ◽  
Free Living

ABSTRACTSoil bacteria called rhizobia trigger the formation of root nodules on legume plants. The rhizobia infect these symbiotic organs and adopt an intracellular lifestyle within the nodule cells, where they differentiate into nitrogen-fixing bacteroids. Several legume lineages force their symbionts into an extreme cellular differentiation, comprising cell enlargement and genome endoreduplication. The antimicrobial peptide transporter BclA is a major determinant of this process inBradyrhizobiumsp. strain ORS285, a symbiont ofAeschynomenespp. In the absence of BclA, the bacteria proceed until the intracellular infection of nodule cells, but they cannot differentiate into enlarged polyploid and functional bacteroids. Thus, thebclAnodule bacteria constitute an intermediate stage between the free-living soil bacteria and the nitrogen-fixing bacteroids. Metabolomics on whole nodules ofAeschynomene afrasperaandAeschynomene indicainfected with the wild type or thebclAmutant revealed 47 metabolites that differentially accumulated concomitantly with bacteroid differentiation. Bacterial transcriptome analysis of these nodules demonstrated that the intracellular settling of the rhizobia in the symbiotic nodule cells is accompanied by a first transcriptome switch involving several hundred upregulated and downregulated genes and a second switch accompanying the bacteroid differentiation, involving fewer genes but ones that are expressed to extremely elevated levels. The transcriptomes further suggested a dynamic role for oxygen and redox regulation of gene expression during nodule formation and a nonsymbiotic function of BclA. Together, our data uncover the metabolic and gene expression changes that accompany the transition from intracellular bacteria into differentiated nitrogen-fixing bacteroids.IMPORTANCELegume-rhizobium symbiosis is a major ecological process, fueling the biogeochemical nitrogen cycle with reduced nitrogen. It also represents a promising strategy to reduce the use of chemical nitrogen fertilizers in agriculture, thereby improving its sustainability. This interaction leads to the intracellular accommodation of rhizobia within plant cells of symbiotic organs, where they differentiate into nitrogen-fixing bacteroids. In specific legume clades, this differentiation process requires the bacterial transporter BclA to counteract antimicrobial peptides produced by the host. Transcriptome analysis ofBradyrhizobiumwild-type andbclAmutant bacteria in culture and in symbiosis withAeschynomenehost plants dissected the bacterial transcriptional response in distinct phases and highlighted functions of the transporter in the free-living stage of the bacterial life cycle.

scholarly journals Promoter Proximal Pausing Limits Tumorous Growth Induced by the Yki Transcription Factor in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (1) ◽  
pp. 67-77 ◽  
Author(s):  
Sanket Nagarkar ◽  
Ruchi Wasnik ◽  
Pravallika Govada ◽  
Stephen Cohen ◽  
L. S. Shashidhara
Keyword(s):  
Gene Expression ◽  
Rna Polymerase Ii ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Elongation Factor ◽  
Imaginal Discs ◽  
Link Type ◽  
Genome Wide ◽  
Wing Imaginal Discs ◽  
Tumorous Growth

Promoter proximal pausing (PPP) of RNA polymerase II has emerged as a crucial rate-limiting step in the regulation of gene expression. Regulation of PPP is brought about by complexes 7SK snRNP, P-TEFb (Cdk9/cycT), and the negative elongation factor (NELF), which are highly conserved from Drosophila to humans. Here, we show that RNAi-mediated depletion of bin3 or Hexim of the 7SK snRNP complex or depletion of individual components of the NELF complex enhances Yki-driven growth, leading to neoplastic transformation of Drosophila wing imaginal discs. We also show that increased CDK9 expression cooperates with Yki in driving neoplastic growth. Interestingly, overexpression of CDK9 on its own or in the background of depletion of one of the components of 7SK snRNP or the NELF complex necessarily, and specifically, needed Yki overexpression to cause tumorous growth. Genome-wide gene expression analyses suggested that deregulation of protein homeostasis is associated with tumorous growth of wing imaginal discs. As both Fat/Hippo/Yki pathway and PPP are highly conserved, our observations may provide insights into mechanisms of oncogenic function of YAP—the ortholog of Yki in humans.

scholarly journals The Role of lncRNAs in Gene Expression Regulation through mRNA Stabilization

2021 ◽  
Vol 7 (1) ◽  
pp. 3
Author(s):  
Maialen Sebastian-delaCruz ◽  
Itziar Gonzalez-Moro ◽  
Ane Olazagoitia-Garmendia ◽  
Ainara Castellanos-Rubio ◽  
Izortze Santin
Keyword(s):  
Gene Expression ◽  
Mrna Stability ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Gene Expression Regulation ◽  
Rna Binding Proteins ◽  
Regulation Of Gene Expression ◽  
Mrna Stabilization ◽  
Living Organisms ◽  
Almost All

mRNA stability influences gene expression and translation in almost all living organisms, and the levels of mRNA molecules in the cell are determined by a balance between production and decay. Maintaining an accurate balance is crucial for the correct function of a wide variety of biological processes and to maintain an appropriate cellular homeostasis. Long non-coding RNAs (lncRNAs) have been shown to participate in the regulation of gene expression through different molecular mechanisms, including mRNA stabilization. In this review we provide an overview on the molecular mechanisms by which lncRNAs modulate mRNA stability and decay. We focus on how lncRNAs interact with RNA binding proteins and microRNAs to avoid mRNA degradation, and also on how lncRNAs modulate epitranscriptomic marks that directly impact on mRNA stability.

scholarly journals A description of the relationship in healthy longevity and aging-related disease: from gene to protein

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Xiaolin Ni ◽  
Zhaoping Wang ◽  
Danni Gao ◽  
Huiping Yuan ◽  
Liang Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prolonged Exposure ◽  
Gene Expression Regulation ◽  
Regulation Of Gene Expression ◽  
Human Longevity ◽  
Form Complex ◽  
Genetic Characteristics ◽  
Age Related ◽  
The Relationship

AbstractHuman longevity is a complex phenotype influenced by both genetic and environmental factors. It is also known to be associated with various types of age-related diseases, such as Alzheimer’s disease (AD) and cardiovascular disease (CVD). The central dogma of molecular biology demonstrates the conversion of DNA to RNA to the encoded protein. These proteins interact to form complex cell signaling pathways, which perform various biological functions. With prolonged exposure to the environment, the in vivo homeostasis adapts to the changes, and finally, humans adopt the phenotype of longevity or aging-related diseases. In this review, we focus on two different states: longevity and aging-related diseases, including CVD and AD, to discuss the relationship between genetic characteristics, including gene variation, the level of gene expression, regulation of gene expression, the level of protein expression, both genetic and environmental influences and homeostasis based on these phenotypes shown in organisms.

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