Affymetrix expression profiling was used to evaluate the association between IL13R2 expression, and mesenchymal, proneural, classical and neural signature genes expression for glioma subclasses defined by Verhaak et al (Cancer Cell; 2010).
Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.
Cell line, Treatment
View SamplesMuch has been learned about transcriptional cascades and networks from large-scale systems analyses of high-throughput data sets. However, analysis methods that optimize statistical power through simultaneous evaluation of thousands of ChIP-seq peaks or differentially expressed genes possess substantial limitations in their ability to uncover mechanistic principles of transcriptional control. By examining nascent transcript RNA-seq, ChIP-seq, and binding motif data sets from lipid A-stimulated macrophages with increased attention to the quantitative distribution of signals, we identified unexpected relationships between the in vivo binding properties of inducible transcription factors, motif strength, and transcription. Furthermore, rather than emphasizing common features of large clusters of co-regulated genes, our results highlight the extent to which unique mechanisms regulate individual genes with key biological functions. Our findings demonstrate the mechanistic value of stringent interrogation of well- defined sets of genes as a complement to broader systems analyses of transcriptional cascades and networks. Overall design: Bone marrow-derived macrophages derived from C57Bl/6, Myd88-/-, Trif-/-, Irf3-/-, Ifnar-/-, and RelA-/- mice were stimulated with lipid A; C57Bl/6 macrophages were stimulated with lipid A in the presence of MAPK inhibitors or cycloheximide, or stimulated with PAM3CSK4 for 0, 15, 30, 60, and 120 minutes, or stimulated with lipid A for 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 minutes. Two biological replicates were generated for each time point for each treatment type.
A Stringent Systems Approach Uncovers Gene-Specific Mechanisms Regulating Inflammation.
No sample metadata fields
View SamplesIn adipocyte-specific knockout mice (Bcl6AKO), we found that Bcl6 deletion results in strikingly increased inguinal but not perigonadal adipocyte size and tissue mass in addition to marked insulin sensitivity. Genome-wide DNA binding and RNA expression analyses revealed that BCL6 controls gene networks involved in cell growth and fatty acid biosynthesis. Thus, our studies identify BCL6 as a negative regulator of subcutaneous adipose tissue expansion and metabolic health. Overall design: Identification of adipocyte BCL6-regulated genes
Loss of Transcriptional Repression by BCL6 Confers Insulin Sensitivity in the Setting of Obesity.
Sex, Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.
Specimen part
View SamplesNeurons utilize glucose to generate adenosine triphosphate (ATP) essential for their survival, excitability and synaptic signaling, as well as initiating changes in neuronal structure and function. Defects in oxidative metabolism and mitochondria functions are also associated with aging and diverse human neurological diseases1-4. While neurons are known to adapt their metabolism to meet the increased energy demands of complex behaviors such as learning and memory, the molecular underpinnings regulating this process remain poorly understood4-6. Here we show that the orphan nuclear receptor estrogen related receptor gamma (ERR) becomes highly expressed during retinoic-acid induced neurogenesis and is widely expressed in neuronal nuclei throughout the brain. Mechanistically, we show that ERR directly orchestrates the expression of networks of genes involved in mitochondrial oxidative phosphorylation and energy generation in neurons. The importance of this regulation is evidenced by decreased adaptive metabolic capacity in cultured neurons lacking ERR, and reduced long-term potentiation (LTP) in ERR-/- hippocampal slices. Notably, the defect in LTP was rescued by the metabolic intermediate pyruvate, functionally linking the ERR knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERR exhibit defects in spatial learning and memory. These findings implicate ERR in the metabolic adaptations required for long-term memory formation.
Dependence of hippocampal function on ERRγ-regulated mitochondrial metabolism.
Specimen part
View SamplesSMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point.
SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis.
No sample metadata fields
View SamplesThe transcriptional co-regulator IRF2BP1 gets de-SUMOylated after EGF treatment in Hela cells. SUMOylation of IRF2BP1 occurs at position K579.
Transient deSUMOylation of IRF2BP proteins controls early transcription in EGFR signaling.
Cell line, Treatment
View SamplesFollicular lymphoma (FL) is an indolent lymphoma associated with follicular center B cells, and typically contains the Bcl-2 chromosomal translocation t(14;18), which leads to overexpression of the anti-apoptotic intracellular protein Bcl-2. FLs are sensitive to chemotherapy; however, patient relapses occur and response duration becomes progressively shorter, with the majority of patients eventually dying from the disease. Enzastaurin (LY317615), an acyclic bisindolylmaleimide, was initially developed as an ATP-competitive selective inhibitor of PKC. We found, in agreement with recent reports, that enzastaurin inhibits cell proliferation and induces apoptosis. These results are consistent with decreased phosphorylation of the Akt pathway and its downstream targets. To provide new insights into the anti-tumor action of enzastaurin on non-Hodgkin lymphoma, we investigated its effects on gene expression profiles of the B cell lymphoma RL cell line by oligonucleotide microarray analysis. We identified a set of 41 differentially expressed genes, mainly involved in cellular adhesion, apoptosis, inflammation, and immune and defense responses. These observations provide new insights into the mechanisms involved in the induction of apoptosis by enzastaurin in B cell lymphoma cell lines, and identify possible pathways that may contribute to the induction of apoptosis.
Genomic profiling of enzastaurin-treated B cell lymphoma RL cells.
Specimen part, Cell line, Treatment
View SamplesCutaneous sarcoidosis skin provides relatively non invasive access to granulomatous sarcoidosis tissue.
Molecular profiling and gene expression analysis in cutaneous sarcoidosis: the role of interleukin-12, interleukin-23, and the T-helper 17 pathway.
Subject
View SamplesThe Anopheles gambiae midgut harbors bacteria that proliferate upon a blood feed. We used microarrays to examine the midgut gene expression response at early stages (3hours) after an artifitial meal containing heat killed bacteria.
A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.
Age, Specimen part
View Samples