This SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Specimen part
View SamplesThe aim of this dataset was to study in detail the transcription kinetics initiated by cytokine IL-4 in early differentiation of Th2 cells.
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Specimen part
View SamplesSTAT6 is a major transcription factor driving the polarization of Th2 cells in response to cytokine IL-4. Here we have analyzed on a genome wide level the STAT6 mediated gene expression after IL-4 induction in naive human CD4+ T cells. RNAi mediated STAT6 knockdown was used to reveal the genes specifically regulated by STAT6.
Genome-wide profiling of interleukin-4 and STAT6 transcription factor regulation of human Th2 cell programming.
Specimen part
View SamplesDietary lipids and gut microbiota may both influence adipose tissue physiology. By feeding conventional and germ-free mice high fat diets with different lipid compositon we aimed to investigate how dietary lipids and the gut microbiota interact to influence inflammation and metabolism in the liver
Interaction between dietary lipids and gut microbiota regulates hepatic cholesterol metabolism.
Age, Specimen part
View SamplesBorrelia burgdorferi, the agent of Lyme disease, promotes pro-inflammatory changes in endothelium that lead to the recruitment of leukocytes. The host immune response to infection results in increased levels of IFN-gamma in the serum and lesions of Lyme disease patients that correlate with greater severity of disease. Therefore, the effect of IFN-gamma on the gene expression profile of primary human endothelial cells exposed to B. burgdorferi was determined. B. burgdorferi and IFN-gamma synergistically augmented the expression of 34 genes, seven of which encode chemokines. Six of these (CCL7, CCL8, CX3CL1, CXCL9, CXCL10, and CXCL11) attract T lymphocytes, and one (CXCL2) is specific for neutrophils. Synergistic production of the attractants for T cells was confirmed at the protein level. IL-1beta, TNF-alpha, and LPS also cooperated with IFN-gamma to induce synergistic production of CXCL10 by endothelium, indicating that IFN-gamma potentiates inflammation in concert with a variety of mediators. An in vitro model of the blood vessel wall revealed that an increased number of human T lymphocytes traversed endothelium exposed to B. burgdorferi and IFN-gamma, as compared to unstimulated endothelial monolayers. In contrast, addition of IFN-gamma diminished the migration of neutrophils across B. burgdorferi-activated endothelium. IFN-gamma thus alters gene expression by endothelium exposed to B. burgdorferi in a manner that promotes recruitment of T cells and suppresses that of neutrophils. This modulation may facilitate the development of chronic inflammatory lesions in Lyme disease.
IFN-gamma alters the response of Borrelia burgdorferi-activated endothelium to favor chronic inflammation.
No sample metadata fields
View SamplesAssessment of p53 targets by gene expression array analysis in irradiated and nonirradiated Wip1+/+ and Wip1-/- MEFs.
The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop.
Specimen part, Treatment
View SamplesA new method to measure elongation and intitiation rates Overall design: Reversal inhibition of transcription with DRB and tagging newly transcribed RNA with 4-thiouridine (4sU)
4sUDRB-seq: measuring genomewide transcriptional elongation rates and initiation frequencies within cells.
No sample metadata fields
View SamplesWe were interested to explain why p53 binds some high affinity sites in contrast to other high affinity sites that are not bound by p53.
p53 binds preferentially to genomic regions with high DNA-encoded nucleosome occupancy.
Cell line, Treatment
View Samplesp53 is a pivotal tumor suppressor and a major barrier against cancer. We now report that silencing of the Hippo pathway tumor suppressors LATS1 and LATS2 in non-transformed mammary epithelial cells reduces p53 phosphorylation and increases its association with the p52 NF-?B subunit. Moreover, it partly shifts p53’s conformation and transcriptional output towards a state resembling cancer-associated p53 mutants, and endow p53 with the ability to promote cell migration. Notably, LATS1 and LATS2 are frequently downregulated in breast cancer; we propose that such downregulation might benefit cancer by converting p53 from a tumor suppressor into a tumor facilitator. Overall design: MCF10A cells transfected with siRNA against LATS1/2 alone, p53 alone or LATS1/2 and p53 together. Two independent MCF10A batches provided biological replicates
Down-regulation of LATS kinases alters p53 to promote cell migration.
No sample metadata fields
View SamplesChromosomal instability in early cancer stages is caused by stress on DNA replication. The molecular basis for replication perturbation in this context is currently unknown. We studied the replication dynamics in cells in which a regulator of S-phase entry and cell proliferation, the Rb-E2F pathway, is aberrantly activated. Aberrant activation of this pathway by HPV-16 E6/E7 or cyclin E oncogenes, significantly decreased the cellular nucleotide levels in the newly transformed cells. Exogenously supplied nucleosides rescued the replication stress and DNA damage, and dramatically decreased oncogene-induced transformation. Increased transcription of nucleotide biosynthesis genes, mediated by expressing the transcription factor c-Myc, increased the nucleotide pool and also rescued the replication-induced DNA damage. Our results suggest a model for early oncogenesis in which uncoordinated activation of factors regulating cell proliferation leads to insufficient nucleotides that fail to support normal replication and genome stability.
Nucleotide deficiency promotes genomic instability in early stages of cancer development.
Sex, Specimen part
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