This SuperSeries is composed of the SubSeries listed below.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View SamplesTo gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View SamplesUrothelial cell carcinoma of the bladder (UCC) is a common disease characterized by FGFR3 mutation. Whilst upregulation of this oncogene occurs most frequently in low-grade non-invasive tumors, recent data reveal increased FGFR3 expression characterizes a common sub-type of invasive UCC sharing genetic similarities with lobular breast cancer. These similarities include upregulation of the FOXA1 transcription factor and reduced expression of microRNAs-99a/100. We have previously identified direct regulation of FGFR3 by these two microRNAs and now search for further targets. Using a microarray meta-database we find potential FOXA1 regulation by microRNAs-99a/100. We confirm direct targeting of the FOXA1 3UTR by microRNAs-99a/100 and also potential indirect regulation through microRNA-485-5p/SOX5/JUN-D/FOXL1 and microRNA-486/FOXO1a. In 292 benign and malignant urothelial samples, we find an inverse correlation between the expression of FOXA1 and microRNAs-99a/100 (r=-0.33 to -0.43, p<0.05). As for FGFR3 in UCC, tumors with high FOXA1 expression have lower rates of progression than those with low expression (Log rank p=0.009). Using global gene expression and CpG methylation profiling we find genotypic consequences of FOXA1 upregulation in UCC. These are associated with regional hypomethylation and near FOXA1 binding sites, and mirror patterns previously reported in FGFR3 mutant UCC. These include gene silencing through aberrant hypermethylation (e.g. IGFBP3) and affect genes that characterize lobular breast cancer (e.g. ERBB2, XBP1). In conclusion, we have identified microRNAs-99a/100 mediate a direct relationship between FGFR3 and FOXA1, and potentially facilitate cross talk between these pathways in UCC.
MicroRNA-99a and 100 mediated upregulation of FOXA1 in bladder cancer.
Cell line
View SamplesDendritic cells (DCs) process and present self and foreign antigens to induce tolerance or immunity. In vitro models suggest that induction of immunity is controlled by regulating the presentation of antigen, but little is known about how DCs control antigen presentation in vivo. To examine antigen processing and presentation in vivo we specifically targeted antigens to the two major subsets of DCs using chimeric monoclonal antibodies. Unlike CD8+ DCs that express the cell surface protein CD205, CD8- DCs, which are positive for the 33D1 antigen, are specialized for presentation on MHC class II. This difference in antigen processing is intrinsic to the DC subsets and associated with increased expression of proteins associated with MHC processing.
Differential antigen processing by dendritic cell subsets in vivo.
No sample metadata fields
View SamplesIt is known that natural killer (NK) cells are a heterogeneous population of functionally distinct NK cell subsets. Here we report on different genomic, phenotypic and functional properties of human NK cell subsets derived from peripheral blood, thymus and bone marrow. NK cell subpopulations were defined via expression of CD56 and CD16.
Specific phenotype and function of CD56-expressing innate immune cell subsets in human thymus.
Specimen part
View SamplesPowdery mildew, caused by the fungus Blumeria graminis (DC) Speer, is one of the most important foliar diseases of cereals worldwide. It is an obligate biotrophic parasite, colonising leaf epidermal cells to obtain nutrients from the plant cells without killing them. Syringolin A (sylA), a circular peptide secreted by the phytopathogenic bacterium Pseudomonas syringae pv. syringae, triggers a hypersensitive cell death reaction (HR) at infection sites when sprayed onto powdery mildew infected wheat which essentially eradicates the fungus. The rational was to identify genes whose expression was specifically regulated during HR, i.e. genes that might be involved in the switch of compatibility to incompatibility.<br></br>Powdery mildew-infected or uninfected plants were treated with syringolin two days after infection and plant material for RNA extraction was collected at 0.5, 1, 2, 4, 8, 12 hours after treatment (hat), resulting in an early (2 and 4 hat) and late pool (8 and 12 hat). Plant material that was uninfected prior to syringolin treatment was collected 8 and 12 hat (late pool of uninfected plant material), and 1 hat, respectively.
Transcriptional changes in powdery mildew infected wheat and Arabidopsis leaves undergoing syringolin-triggered hypersensitive cell death at infection sites.
Compound, Time
View SamplesOlfactory sensory neurons express just one out of a possible ~1000 odorant receptor genes, reflecting an exquisite mode of gene regulation. In one model, once an odorant receptor is chosen for expression, other receptor genes are suppressed by a negative feedback mechanism, ensuring a stable functional identity of the sensory neuron for the lifetime of the cell. The signal transduction mechanism subserving odorant receptor gene silencing remains obscure, however. Here we demonstrate in the zebrafish that odorant receptor gene silencing is dependent on receptor activity. Moreover, we show that signaling through G protein ß? subunits is both necessary and sufficient to suppress the expression of odorant receptor genes, and likely acts through histone methylation to maintain the silenced odorant receptor genes in transcriptionally inactive heterochromatin. These results provide new insights linking receptor activity with the epigenetic mechanisms responsible for ensuring the expression of one odorant receptor per olfactory sensory neuron. Overall design: Total 6 samples were analyzed-3 controls & 3 samples
Normalization of RNA-seq data using factor analysis of control genes or samples.
No sample metadata fields
View Samplestranscriptome profiling of miR-92a inhibitor treated and control cells with the aim of measuring miR-92a influence on its mRNA targets
Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding.
Cell line, Treatment
View SamplesLuminal breast cancers express estrogen (ER) and progesterone (PR) receptors, and respond to endocrine therapies. However, some ER+PR+ tumors display intrinsic or acquired resistance, possibly related to PR. Two PR isoforms, PR-A and PR-B, regulate distinct gene subsets that may differentially influence tumor fate. A high PR-A:PR-B ratio is associated with poor prognosis and tamoxifen resistance. We speculate that excessive PR-A marks tumors that will relapse early. Here we address mechanisms by which PR-A regulate transcription, focusing on SUMOylation. We use receptor mutants and synthetic promoter/reporters to show that SUMOylation deficiency or the deSUMOylase SENP1 enhance transcription by PR-A, independent of the receptors dimerization interface or DNA binding domain. De-SUMOylation exposes the agonist properties of the antiprogestin RU486. Thus, on synthetic promoters, SUMOylation functions as an independent brake on transcription by PR-A. What about PR-A SUMOylation of endogenous human breast cancer genes? To study these, we used gene expression profiling. Surprisingly, PR-A SUMOylation influences progestin target genes differentially, with some upregulated, others downregulated, and others unaffected. Hormone-independent gene regulation is also PR-A SUMOylation dependent. Several SUMOylated genes were analyzed in clinical breast cancer database. In sum, we show that SUMOylation does not simply repress PR-A. Rather, it regulates PR-A activity in a target selective manner including genes associated with poor prognosis, shortened survival, and metastasis.
SUMOylation Regulates Transcription by the Progesterone Receptor A Isoform in a Target Gene Selective Manner.
Specimen part, Treatment
View SamplesPurpose:To dissect the mechanisms underlying altered gene expression in aneuploids, we measured transcript abundance in colonies of haploid yeast strain F45 and derived strains, including strains disomic for chromosomes XV and XVI, using RNA-seq. F45 colonies display complex “fluffy” morphologies, while the disomic colonies are smooth, resembling laboratory strains Methods: RNA-seq analysis was carried out on RNA isolated from fully developed S. cerevisiae colonies, grown on solid medium for four days, either in triplicate or quadruplicate. Stranded, paired-end sequencing was carried out in two batches. In the first batch 2x51 bp sequencing was carried out on an Illumina Hiseq2000 and in the second batch 2x75 bp sequencing was carried out on an Illumina NextSeq. Readpairs were aligned using Bowtie2 (version 2.1.0)with the parameters [-N 1 -I 50 -X 450 -p 6 --reorder -x -S] and allowing 1 mismatch per read. Differential transcription was detected and quantified using EdgeR (v. 3.6.8) Results: Our two disomes displayed similar transcriptional profiles, a phenomenon not driven by their shared smooth colony morphology nor specified purely by the karyotype. Surprisingly, the environmental stress response (ESR) was induced in euploid F45, relative to the two disomes, rather than vice-versa. We also identified genes whose expression reflected a non-linear interaction between the copy number of a transcriptional regulatory gene on chromosome XVI, DIG1, and the copy number of other chromosome XVI genes. DIG1 and the remaining chromosome XVI genes also demonstrated distinct contributions to the effect of the chromosome XVI disome on ESR gene expression. Conclusions: Expression changes in aneuploids reflect a mixture of effects shared between different aneuploidies, including stress responses, and effects unique to perturbing the copy number of particular chromosomes, including non-linear copy number interactions between genes. The balance between these two phenomena is likely to be genotype and environment specific. Overall design: mRNA profiles of 4 day old haploid F45 colonies, and colonies derived from F45 were generated by deep sequencing, in triplicate or quadruplicate, using Illumina Hiseq2000 or Illumina Nextseq sequencing.
Transcriptional Profiling of Biofilm Regulators Identified by an Overexpression Screen in <i>Saccharomyces cerevisiae</i>.
Cell line, Subject
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