Long chain fatty acids (LCFA) serve as energy sources, components of cell membranes, and precursors for signalling molecules. Here we show that these important biological compounds also regulate gene expression by controlling the transcriptional activities of the retinoic acid (RA)-activated nuclear receptors RAR and PPAR/. Our data indicates that these activities of LCFA are mediated by FABP5, a protein that delivers ligands from the cytosol to nuclear PPAR/. Both saturated and unsaturated LCFA (SLCFA, ULCFA) tightly bind to FABP5, thereby displacing RA and diverting it to RAR. However, while SLCFA inhibit, ULCFA activate the FABP5/PPAR/ pathway. By concomitantly promoting the activation of RAR and inhibiting the activity of PPAR/, SLCFA suppress the growth and oncogenic properties of FABP5-expressing carcinoma cells both in cultured cells and in vivo.
Saturated fatty acids regulate retinoic acid signalling and suppress tumorigenesis by targeting fatty acid-binding protein 5.
Cell line
View SamplesIn most organisms biological processes are partitioned, or phased to specific times over the day through interactions between external cycles of temperature (thermocycles) and light (photocycles), and the endogenous circadian clock. This orchestration of biological activities is achieved in part through an underlying transcriptional network. To understand how thermocycles, photocycles and the circadian clock interact to control time of day specific transcript abundance in Arabidopsis thaliana, we conducted four diurnal and three circadian two-day time courses using Affymetrix GeneChips (ATH1). All time courses were carried out with seven-day-old seedlings grown on agar plates under thermocycles (HC, hot/cold) and/or photocycles (LD, light/dark), or continuous conditions (LL, continuous light; DD, continuous dark, HH, continuous hot). Whole seedlings (50-100), including roots, stems and leaves were collected every four hours and frozen in liquid nitrogen. The four time courses interrogating the interaction between thermocycles, photocycles and the circadian clock were carried out as two four-day time courses. Four-day time courses were divided into two days under diurnal conditions, and two days under circadian conditions of continuous light and temperature. Thermocycles of 12 hours at 22C (hot) and 12 hours at 12C (cold) were used in this study. The two time courses interrogating photoperiod were conducted under short days (8 hrs light and 16 hrs dark) or long days (16 hrs light and 8 hrs dark) under constant temperature. In addition, the photoperiod time courses were in the Landsberg erecta (ler) accession, in contrast to the other time courses that are in the Columbia (col) background. The final time course interrogated circadian rhythmicity in seedlings grown completely in the dark (etiolated). Dark grown seedlings were synchronized with thermocycles, and plants were sampled under the circadian conditions of continuous dark and temperature.
Network discovery pipeline elucidates conserved time-of-day-specific cis-regulatory modules.
Age, Time
View SamplesThe irreversible decarboxylation step, which commits 2-oxo acids to the Ehrlich pathway, was initially attributed to pyruvate decarboxylase. However, the yeast genome was shown to harbour no fewer than 5 genes that show sequence similarity with thiamine-diphosphate dependent decarboxylase genes. Three of these (PDC1, PDC5 and PDC6) encode pyruvate decarboxylases { while ARO10 and THI3 represent alternative candidates for Ehrlich-pathway decarboxylases.
The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism.
No sample metadata fields
View SamplesAnalysis of alveolar macrophage gene expression in C57BL6 wild-type and RAGE null mice exposed to cigarette smoke Overall design: 4 groups of 3-4 mice at two exposure time points (7-day and 4 month), 31 samples total
RAGE is a Critical Mediator of Pulmonary Oxidative Stress, Alveolar Macrophage Activation and Emphysema in Response to Cigarette Smoke.
Cell line, Subject, Time
View SamplesThe area postrema (AP) is a sensory circumventricular organ characterised by extensive fenestrated vasculature and neurons which are capable of detecting circulating signals of osmotic, cardiovascular, immune and metabolic status. The AP can communicate these messages via efferent projections to brainstem and hypothalamic structures that are able to orchestrate an appropriate response. We have used microarrays to profile the transcriptome of the AP in the Sprague Dawley (SD) and Wistar Kyoto (WKY) rat and present here a comprehensive catalogue of gene expression, focussing specifically on the population of ion channels, receptors and G protein-coupled receptors (GPCRs) expressed in this sensory tissue; of the GPCRs expressed in the rat AP we identified ~36% that are orphans having no established ligand. We have also looked at the ways in which the AP transcriptome responds to the physiological stressors of 72-hours dehydration (DSD) and 48-hours fasting (FSD) and have performed microarrays under these conditions. Comparison between the DSD and SD or between FSD and SD revealed only a modest number of AP genes that are regulated by these homeostatic challenges. The expression levels of a much larger number of genes are altered in the spontaneously hypertensive rat (SHR) AP compared to the normotensive WKY controls however. Finally, analysis of these hypertension-related elements revealed genes that are involved in both the regulation of blood pressure and immune function and as such are excellent targets for further study.
The transcriptome of the medullary area postrema: the thirsty rat, the hungry rat and the hypertensive rat.
Sex, Specimen part
View SamplesGranulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate that mouse MDPs arose from CMPs independently of GMPs, and that GMPs and MDPs produced monocytes via similar, but distinct, monocyte-committed progenitors. GMPs and MDPs yielded classical (Ly6Chi) monocytes with gene expression signatures that were defined by their origins and impacted their function. GMPs produced a subset of “neutrophil-like” monocytes, whereas MDPs gave rise to a subset of monocytes that yielded monocyte-derived dendritic cells. GMPs and MDPs were also independently mobilized to produce specific combinations of myeloid cell types following the injection of microbial components. Thus, the balance of GMP and MDP differentiation shapes the myeloid cell repertoire during homeostasis and following infection. Overall design: RNA-seq of myeloid progenitors and Ly6Chi monocytes from mouse bone marrow. 4 progenitor fractions (GMPs, MDPs, GPs and a mixed fraction of MPs + cMoPs) were isolated from the pooled bone marrow of 20 mice. GMPs and MDPs were also cultured in vitro and the monocyte-committed progenitors and Ly6Chi monocytes they produced were also harvested. RNA was extracted from the 4 ex vivo progenitor fractions, and the 4 populations derived in vitro (GMP-derived monocyte progenitors = MP; MDP-derived monocyte progenitors = cMoP; GMP-derived Ly6Chi monocytes = G-mono; MDP-derived Ly6Chi monocytes = M-mono). The whole process was repeated using 20 additional mice to obtain a replicate set of samples.
Granulocyte-Monocyte Progenitors and Monocyte-Dendritic Cell Progenitors Independently Produce Functionally Distinct Monocytes.
Specimen part, Cell line, Subject
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified.
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesZinc is indispensable for the catalytic activity and structural stability of many proteins, and its deficiency can have severe consequences for microbial growth in natural and industrial environments. For example, Zn depletion in wort negatively affects beer fermentation and quality. Several studies have investigated yeast adaptation to low Zn supply, but were all performed in batch cultures, where specific growth rate depends on Zn availability. The transcriptional responses to growth-rate and Zn availability are then intertwined, which obscures result interpretation. In the present study, transcriptional responses of Saccharomyces cerevisiae to Zn availability were investigated at a fixed specific growth rate under Zn limitation and excess in chemostat culture. To investigate the context-dependency of this transcriptional response, yeast was grown under several chemostat regimes resulting in various carbon (glucose), nitrogen (ammonium) and oxygen supplies. A robust set of genes that responded consistently to Zn limitation was identified and enabled the definition of a Zn-specific Zap1 regulon comprising of 26 genes and characterized by a broader ZRE consensus (MHHAACCBYNMRGGT) than so far described. Most surprising was the Zn-dependent regulation of genes involved in storage carbohydrate metabolism. Their concerted down-regulation was physiologically relevant as revealed by a substantial decrease in glycogen and trehalose cellular content under Zn limitation. An unexpectedly large amount of genes were synergistically or antagonistically regulated by oxygen and Zn availability. This combinatorial regulation suggested a more prominent involvement of Zn in mitochondrial biogenesis and function than hitherto identified
Physiological and transcriptional responses of Saccharomyces cerevisiae to zinc limitation in chemostat cultures.
No sample metadata fields
View SamplesNon-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.
Sex, Specimen part
View Samples