More than 7% of the Pseudomonas aeruginosa genes are encoding transcriptional regulators, many of which with unknown functions. Among them, those belonging to the LysR family are the most represented. The PA4203 gene lies upstream of the previously characterized ppgL gene (PA4204), which encodes a periplasmic gluconolactonase, which detoxifies gluconolactone by converting it to gluconate. Upstream of PA4203 and in the opposite orientation are the PA4202 gene coding for a nitronate monooxygenase and ddlA (PA4201) encoding a D-alanine alanine ligase. This genetic organization is conserved in all P. aeruginosa genomes, but not in other pseudomonads. The intergenic regions between PA4203 and ppgL, and PA4202 are very short (79 and 107 nucleotides, respectively). PA4203 is a repressor of PA4202 and of its own transcription. A chromatin immunoprecipation analysis confirmed the presence of a single PA4203 binding site between PA4202 and PA4203. Electrophoretic mobility shift assays (EMSAs) with the purified PA4203 protein and in41 gel footprinting with the 1, 10-phenanthroline-copper ion, combined with primer extension analysis to determine transcriptional startpoints allowed the identification of a LysR binding motive in the PA4202 and PA4203 intergenic region. Despite this, a transcriptome analysis revealed more genes to be affected in a PA4203 mutant, likely due to the overexpression of the nitronate monooxygenase (PA4202). Deletion of the PA4202 gene resulted in an increased sensitivity of the cells to 3- nitropropionic acid (3-NPA).
Pseudomonas aeruginosa LysR PA4203 regulator NmoR acts as a repressor of the PA4202 nmoA gene, encoding a nitronate monooxygenase.
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Loss of the Hematopoietic Stem Cell Factor GATA2 in the Osteogenic Lineage Impairs Trabecularization and Mechanical Strength of Bone.
Cell line
View SamplesGATA2 is a transcription factor that is required for hematopoietic stem cell (HSC) differentiation. GATA2 is also expressed in mesenchymal cells and blocks differentiation of both white and brown adipocytes by interfering with C/EBP activity and PPAR expression. By studying genome-wide binding sites of endogenous GATA2 in mesenchymal stem cells (MSC), we discovered a previously unrecognized function of GATA2 in the regulation of skeletal development-related genes. In contrast to hematopoietic stem cells, canonical GATA2 binding motifs in MSCs co-localized with motifs for transcription factors of the FOX and HOX family, known regulators of skeletal development. Consistently, ectopic GATA2 expression in MSCs regulated many osteoblast-related genes. Ectopic GATA2 blocked, whereas GATA2 deletion enhanced differentiation of osteoblastic precursors. GATA2 expression inhibited bone morphogenetic protein (BMP)-2 induced SMAD1/5/8 activity, a pathway that drives osteoblastogenesis. MSC-specific deletion of GATA2 in mice affected both numbers and osteogenic potential of bone-residing precursors without disturbing normal skeletal development. In adult mice, MSC-specific GATA2 deficiency affected trabecular bone structure and its mechanical properties. blood phenotype? In summary, our study identified GATA2 as a novel regulator of osteoblast differentiation and bone morphology, suggesting a role of GATA2 in MSC lineage determination that goes beyond adipocyte differentiation.
Loss of the hematopoietic stem cell factor GATA2 in the osteogenic lineage impairs trabecularization and mechanical strength of bone.
No sample metadata fields
View SamplesRetinol Saturase (RetSat) is an oxidoreductase expressed at high levels in the hepatocyte fraction of liver.
Retinol saturase coordinates liver metabolism by regulating ChREBP activity.
No sample metadata fields
View SamplesIt is unclear how nanosecond electrical pulses affect gene expression.
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Specimen part, Cell line
View SamplesIt is unclear how nanosecond electrical pulses affect gene expression.
Evaluation of the Genetic Response of U937 and Jurkat Cells to 10-Nanosecond Electrical Pulses (nsEP).
Specimen part, Cell line
View SamplesLymph node metastasis is a poor prognosis indicator in esophageal cancer. Although tumor spreading currently forms the main basis for therapy selection, the molecular mechanisms underlying the metastatic pathway remain insufficiently understood. Several studies aimed to investigate these mechanisms but focused mainly on regulatory patterns in the tumors themselves and/or the invaded lymph nodes. To date no study has yet investigated the potential changes on transcription level, which take place within the yet non-invaded niche. Here we provide a comprehensive description of these regulations in patients. In this study the transcriptomic profiles of regional lymph nodes were determined for two patient groups: patients classified as pN1 (metastasis) or pN0 (no metastasis) respectively. All investigated lymph nodes, also those from pN1 patients, were still free of metastasis. The gene expression data was obtained via microarray analysis. Top candidates were validated via PCR and immunohistochemistry. The results show that regional lymph nodes of pN1 patients differ decisively from those of pN0 patients even before metastasis has taken place. In the pN0 group distinct immune response patterns were observed. In contrast, lymph nodes of the pN1 group exhibited a clear profile of reduced immune response and reduced proliferation, but increased apoptosis, enhanced hypoplasia and morphological conversion processes. DKK1 was the most significant gene associated with the molecular mechanisms taking place in lymph nodes of patients suffering from metastasis (pN1). We assume that the two molecular profiles observed constitute two different stages of a progressive disease. Finally we suggest that DKK1 might play an important role within the mechanisms leading to lymph node metastasis.
Molecular changes in pre-metastatic lymph nodes of esophageal cancer patients.
Specimen part, Subject
View SamplesPrecise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established and dynamically maintained and subsequently contribute to transcriptional control are poorly understood. The Swi/Snf (Baf) chromatin remodeling complex is a master developmental regulator and tumor suppressor that is capable of mobilizing nucleosomes in biochemical assays. Yet, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genome-wide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters.
Specimen part
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
View SamplesA clinical study evaluating the dosing of an oral HDACi panobinostat in patient infected with HIV-1. Dosing was 20 mg orally, 3 times weekly, every other week for a total of 8 weeks.
Treatment of HIV-Infected Individuals with the Histone Deacetylase Inhibitor Panobinostat Results in Increased Numbers of Regulatory T Cells and Limits <i>Ex Vivo</i> Lipopolysaccharide-Induced Inflammatory Responses.
Sex
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