scholarly journals Paracrine and autocrine regulation of gene expression by Wnt-inhibitor Dickkopf in wild-type and mutant hepatocytes

2017 ◽  
Vol 11 (1) ◽  
Author(s):  
Niklas Hartung ◽  
Uwe Benary ◽  
Jana Wolf ◽  
Bente Kofahl
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Wild Type ◽  
Autocrine Regulation ◽  
Wnt Inhibitor

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.

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 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 Gene Expression and Regulation from the p7 Promoter of Aedes Densonucleosis Virus

1998 ◽  
Vol 72 (5) ◽  
pp. 4364-4370 ◽  
Author(s):  
Michael W. Kimmick ◽  
Boris N. Afanasiev ◽  
Barry J. Beaty ◽  
Jonathan O. Carlson
Keyword(s):  
Gene Expression ◽  
Translational Regulation ◽  
Transcriptional Control ◽  
Regulation Of Gene Expression ◽  
Open Reading Frames ◽  
Gene Expression And Regulation ◽  
Wild Type ◽  
Nonstructural Proteins ◽  
Study Gene Expression ◽  
Reading Frames

ABSTRACT The nonstructural proteins NS1 and NS2 are thought to be expressed from the p7 promoter of Aedes densonucleosis virus (AeDNV). To study gene expression from the p7 promoter, eight different plasmids were constructed by fusing β-galactosidase or β-glucuronidase into the genome so that the reporter gene was in different open reading frames and under the transcriptional control of the p7 promoter. After transfection into C6/36 Aedes albopictus cells, constructs generated comparable amounts of RNA, but only the NS1 and NS2 fusion constructs produced appreciable levels of active enzyme. NS1 and NS2 fusion constructs contained wild-type AeDNV sequences from the p7 promoter downstream to nucleotide 458. The remaining constructs, with the exception of p7GUS.rf3, lacked some or all of these necessary sequences and inefficiently produced protein. These data suggest that sequences downstream of the p7 promoter play a role in translational regulation of gene expression from the p7 promoter of AeDNV.

scholarly journals Genome Architecture of the Human β-Globin Locus Affects Developmental Regulation of Gene Expression

2005 ◽  
Vol 25 (20) ◽  
pp. 8765-8778 ◽  
Author(s):  
Susanna Harju ◽  
Patrick A. Navas ◽  
George Stamatoyannopoulos ◽  
Kenneth R. Peterson
Keyword(s):  
Gene Expression ◽  
Gene Order ◽  
Yeast Artificial Chromosome ◽  
Fetal Liver ◽  
Globin Gene ◽  
Regulation Of Gene Expression ◽  
Globin Genes ◽  
Wild Type ◽  
Globin Mrna ◽  
Definitive Erythropoiesis

ABSTRACT To test the role of gene order in globin gene expression, mutant human β-globin locus yeast artificial chromosome constructs were used, each having one additional globin gene encoding a “marked” transcript (εm, γm, or βm) integrated at different locations within the locus. When a βm-globin gene was placed between the locus control region (LCR) and the ε-globin gene, βm-globin expression dominated primitive and definitive erythropoiesis; only βm-globin mRNA was detected during the fetal and adult definitive stages of erythropoiesis. When an Aγm-globin gene was placed at the same location, Aγm-globin was expressed during embryonic erythropoiesis and the fetal liver stage of definitive erythropoiesis but was silenced during the adult stage. The downstream wild-type γ-globin genes were not expressed. When an εm-globin gene was placed between the δ- and β-globin genes, it remained silent during embryonic erythropoiesis; only the LCR-proximal wild-type ε-globin gene was expressed. Placement of a βm-globin gene upstream of the Gγ-globin gene resulted in expression of βm-globin in embryonic cells and in a significant decrease in expression of the downstream wild-type β-globin gene. These results indicate that distance from the LCR, an inherent property of spatial gene order, is a major determinant of temporal gene expression during development.

scholarly journals RNase L Is Involved in Liposaccharide-Induced Lung Inflammation

Viruses ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 73
Author(s):  
Ruhan Wei ◽  
Guanmin Chen ◽  
Naseh Algehainy ◽  
Chun Zeng ◽  
Chunfang Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Cell Proliferation ◽  
Acute Lung Injury ◽  
Lung Inflammation ◽  
Regulation Of Gene Expression ◽  
Rnase L ◽  
Wild Type ◽  
Tlr4 Signaling Pathway

RNase L mediates interferon (IFN) function during viral infection and cell proliferation. Furthermore, the role of RNase L in the regulation of gene expression, cell apoptosis, autophagy, and innate immunity has been well established in the last decade. Tissue distribution reveals that RNase L is highly expressed in the lung and other organs. However, the physiological roles of RNase L in the lung are largely unknown. In this study, we found that polysaccharide (LPS)-induced acute lung injury (ALI) was remarkably intensified in mice deficient in RNase L compared to wild type mice under the same condition. Furthermore, we found that RNase L mediated the TLR4 signaling pathway, and regulated the expression of various pro- and anti-inflammatory genes in the lung tissue and blood. Most importantly, RNase L function in macrophages during LPS stimulation may be independent of the 2-5A system. These findings demonstrate a novel role of RNase L in the immune response via an atypical molecular mechanism.

scholarly journals Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element.

1992 ◽  
Vol 6 (7) ◽  
pp. 1143-1152 ◽  
Author(s):  
G P Zambetti ◽  
J Bargonetti ◽  
K Walker ◽  
C Prives ◽  
A J Levine
Keyword(s):  
Gene Expression ◽  
Dna Sequence ◽  
Regulation Of Gene Expression ◽  
Wild Type ◽  
Positive Regulation ◽  
Sequence Element ◽  
Wild Type P53

scholarly journals Cohesin residency determines chromatin loop patterns

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Lorenzo Costantino ◽  
Tsung-Han S Hsieh ◽  
Rebecca Lamothe ◽  
Xavier Darzacq ◽  
Douglas Koshland
Keyword(s):  
Gene Expression ◽  
Chromosome Segregation ◽  
Mammalian Cells ◽  
Regulation Of Gene Expression ◽  
S Phase ◽  
Chromatin Loop ◽  
Wild Type ◽  
Genome Wide ◽  
Mutant Cells ◽  
Order Structures

The organization of chromatin into higher order structures is essential for chromosome segregation, the repair of DNA-damage, and the regulation of gene expression. Using Micro-C XL to detect chromosomal interactions, we observed the pervasive presence of cohesin-dependent loops with defined positions throughout the genome of budding yeast, as seen in mammalian cells. In early S phase, cohesin stably binds to cohesin associated regions (CARs) genome-wide. Subsequently, positioned loops accumulate with CARs at the bases of the loops. Cohesin regulators Wpl1 and Pds5 alter the levels and distribution of cohesin at CARs, changing the pattern of positioned loops. From these observations, we propose that cohesin with loop extrusion activity is stopped by preexisting CAR-bound cohesins, generating positioned loops. The patterns of loops observed in a population of wild-type and mutant cells can be explained by this mechanism, coupled with a heterogeneous residency of cohesin at CARs in individual cells.

scholarly journals Organism-wide single-cell transcriptomics of long-lived C. elegans daf-2-/- mutants reveals tissue-specific reprogramming of gene expression networks

2019 ◽  
Author(s):  
Jessica L. Preston ◽  
Nicholas Stiffler ◽  
Maggie Weitzman
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Expression Profiles ◽  
Regulation Of Gene Expression ◽  
Gene Expression Profiles ◽  
Machine Learning Algorithms ◽  
Wild Type ◽  
Tissue Specific ◽  
C Elegans ◽  
Specific Regulation

AbstractA critical requirement for a systems-level understanding of complex biological processes such as aging is the ability to directly characterize interactions between cells and tissues within a multicellular organism. C. elegans nematodes harboring mutations in the insulin-like receptor daf-2 exhibit dramatically-increased lifespans. To identify tissue-specific biochemical mechanisms regulating aging plasticity, we single-cell sequenced 3’-mRNA libraries generated from seven populations of whole day-one adult wild-type and daf-2-/- worms using the 10x ChromiumV1™platform. The age-synchronized samples were bioinformatically merged into a single aligned dataset containing 40,000 age-synchronized wild-type and daf-2-/- cellular transcriptomes partitioned into 101 clusters, using unsupervised machine-learning algorithms to identify common cell types. Here we describe the basic features of the adult C. elegans single-cell transcriptome and summarize functional alterations observed in the gene expression profiles of long-lived daf-2-/- worms. Comprehensive methods and datasets are provided. This is the first study to directly quantify cell-specific differential gene expression between two age-synchronized, genetically-distinct populations of multicellular organisms. This novel approach answers fundamental questions regarding tissue-specific regulation of gene expression and helps to establish a foundation for a comprehensive C. elegans single-cell gene expression atlas.

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