We 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 SamplesWe report nuclear receptor Esrrb''s responsive genes with or without Esrrb ligand DY131 in DU145 cells. Using Esrrb-null cells, we used RNA-Seq to find Esrrb responsive genes. In addition, we tested DY131-driven Esrrb-dependent genes to test the ligand dependency of Esrrb in regulating gene expression. Overall design: Control vector transfected cells with vehicle treatment, Esrrb expression vector transfected cell with vehicle treatment, control vector transfected cells with DY131 treatment, Esrrb expression vector transfected cell with DY131 treatment.
Messenger RNA profile analysis deciphers new Esrrb responsive genes in prostate cancer cells.
No sample metadata fields
View SamplesWe report Hedgehog signaling responsive genes with or without Esrrb in NI3T3 cells. Using Hh-responsive cells, we used RNA-Seq to find Hh responsive genes. In addition, we tested Esrrb''s modification on Hh target genes'' response. Overall design: Control vector transfected cells with vehicle treatment, Esrrb expression vector transfected cell with vehicle treatment, control vector transfected cells with Hh conditioned medium treatment, Esrrb expression vector transfected cell with Hh conditioned medium treatment,
Genes targeted by the Hedgehog-signaling pathway can be regulated by Estrogen related receptor β.
No sample metadata fields
View Samplesgd T cells recognize unprocessed or non-peptide antigens, respond rapidly to infection, and localize to mucosal surfaces. We have hypothesized that the innate functions of gd T cells may be more similar to those of cells of the myeloid lineage than to other T cells. To begin to test this assumption, we have analyzed the direct response of cultured human and peripheral blood bovine gd T cells to pathogen associated molecular patterns (PAMPs) in the absence of APCs using microarray, real time RT-PCR, proteome array, and chemotaxis assays. Our results indicate that purified gd T cells respond directly to PAMPs by increasing expression of chemokine and activation related genes. The response was distinct from that to known gd T cell antigens and different from the response of myeloid cells to PAMPs. In addition, we have analyzed the expression of a variety of PAMP receptors in gd T cells. Freshly purified bovine gd T cells responded more robustly to PAMPs than did cultured human cells and expressed measurable mRNA encoding a variety of PAMP receptors. Our results suggest that rapid response to PAMPs through the expression of PAMP receptors may be another innate role of gd T cells.
Gamma delta T cells respond directly to pathogen-associated molecular patterns.
No sample metadata fields
View SamplesWorldwide, more than 1 billion people are affected by infestations with soil-transmitted helminths and also in veterinary medicine helminthiases are a severe thread to livestock due to emerging resistances against the common anthelmintics. Proanthocyanidins have been increasingly investigated for their anthelmintic properties, however, except for an interaction with certain proteins of the nematodes, not much is known about their mode of action. To investigate the anthelmintic activity on a molecular level, a transcriptome analysis was performed in Caenorhabditis elegans after treatment with purified and fully characterized oligomeric procyanidins (OPC). The OPCs had previously been obtained from a hydro-ethanolic (1:1) extract from the leaves of Combretum mucronatum, a plant which is traditionally used in West Africa for the treatment of helminthiasis, therefore, also the crude extract was included in the study. Significant changes in differential gene expression were observed mainly for proteins related to the intestine, many of which were located extracellularly or within cellular membranes. Among the up-regulated genes, several hitherto undescribed orthologues of structural proteins in humans were identified, but also genes that are potentially involved in the worms defense against tannins. For example, T22D1.2, an orthologue of human basic salivary proline-rich protein (PRB) 2, and numr-1 (nuclear localized metal responsive) were found to be strongly up-regulated. Down-regulated genes were mainly associated with lysosomal activity, glycoside hydrolysis or the worms innate immune response. No major differences were found between the groups treated with purified OPCs versus the crude extract. Investigations using GFP reporter gene constructs of T22D1.2 and numr-1 corroborated the intestine as the predominant site of the anthelmintic activity.
Transcriptome analysis reveals molecular anthelmintic effects of procyanidins in C. elegans.
Specimen part, Treatment
View SamplesMammalian genomes are promiscuously transcribed, yielding protein-coding and non-coding products. Many transcripts are short-lived due to their nuclear degradation by the ribonucleolytic RNA exosome. Here, we show that abolished nuclear exosome function causes the formation of distinct nuclear foci, containing polyadenylated (pA+) RNA secluded from nucleocytoplasmic export. We asked whether exosome co-factors could serve such nuclear retention. Co-localization studies revealed the enrichment of pA+ RNA foci with 'pA-tail exosome targeting (PAXT) connection' components MTR4, ZFC3H1 and PABPN1, but no overlap with known nuclear structures, such as Cajal bodies, speckles, paraspeckles or nucleoli. Interestingly, ZFC3H1 is required for foci formation, and in its absence selected pA+ RNAs, including coding and non-coding transcripts, are exported to the cytoplasm in a process dependent on the mRNA export factor AlyREF. Our results establish ZFC3H1 as a central nuclear RNA retention factor, counteracting nuclear export activity. Overall design: Nuclear poly(A) selected RNA from HeLa cells was analysed by next generation sequencing upon depletion of EGFP(control) and RNA exosome core factor RRP40
The RNA Exosome Adaptor ZFC3H1 Functionally Competes with Nuclear Export Activity to Retain Target Transcripts.
Specimen part, Subject
View SamplesTranscription profiling by array of pancreas from KrasG12D, Ela-Tgfa and KrasG12D Ela-Tgfa mice
Concomitant pancreatic activation of Kras(G12D) and Tgfa results in cystic papillary neoplasms reminiscent of human IPMN.
Age, Specimen part
View SamplesTo assay the effect of depletion of the RNA exosome on RNAs shorter than the standard length captured by RNA-seq (>200 nt), we created RNA-seq libraries using fragmented RNA and a linker-ligation-based protocol that does not deplete RNAs shorter than 200 nt. Note: these data relate to Figure 6E in Lubas, Andersen et al., Cell Reports 2014 (accepted) Overall design: These samples constitute RNA-seq libraries prepared to enrich for short RNA fragments such as snRNA and snoRNAs. Three different HeLa cell RNAi experiments were used to generate the RNA samples applied in the library construction: control transfected, hRRP40-depleted and triple-depleted of the known RNA exosome-associated ribonucleases (DIS3, DIS3L and hRRP6 knock-down). By these means the data offers reveal RNA exosome substrates via their up-regulation in the respective knock-downs NOTE: The ''Figure6E_RNAseq_DataTable_PlottedValues.txt'' was generated from total 5 samples, with two additional published samples [SRP031620] and provided to better allow readers to fully replicate the analyses presented in the publication.
The human nuclear exosome targeting complex is loaded onto newly synthesized RNA to direct early ribonucleolysis.
No sample metadata fields
View SamplesDBZ (dibenzazepine) treatment in C57BL/6 mice, pancreatic gene expression
Notch signaling is required for exocrine regeneration after acute pancreatitis.
Sex, Age, Specimen part, Disease, Compound, Time
View SamplesWe have analyzed, using DNA microarrays, putative differences in gene-expression level between hereditary BRCA1 mutation-linked and sporadic breast cancer. Our results show that a previously reported marked difference between BRCA1-mutation linked and sporadic breast cancer was probably due to uneven stratification of samples with different ER status and basal-like versus luminal-like subtype. We observed that apparent difference between BRCA1-linked and other types of breast cancer found in univariate analysis was diminished when data were corrected for ER status and molecular subtype in multivariate analyses. In fact, the difference in gene expression pattern of BRCA1-mutated and sporadic cancer is very discrete. These conclusions were supported by the results of Q-PCR validation. We also found that BRCA1 gene inactivation due to promoter hypermethylation had similar effect on general gene expression profile as mutation-induced protein truncation. This suggests that in the molecular studies of hereditary breast cancer, BRCA1 gene methylation should be recognized and considered together with gene mutation.
BRCA1-related gene signature in breast cancer: the role of ER status and molecular type.
Age
View Samples