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SRP044640
Mus musculus
5 Downloadable Samples
Illumina HiSeq 2000
Description
Huntington neurodegenerative disease (HD) is associated with extensive down-regulation of neuronal genes. We show preferential down-regulation of super-enhancer-regulated neuronal function genes in the striatum of HD mice. Striatal super-enhancers display extensive H3K27 acetylation within gene bodies and drive transcription characterized by low levels of paused RNAPII. Down-regulation of gene expression is associated with diminished H3K27 acetylation and RNAPII recruitment. Striatal super-enhancers are enriched in binding motifs for Gata transcription factors, such as Gata2 regulating striatal identity genes. Thus, enhancer topography and transcription dynamics are major parameters determining the propensity of a gene to be deregulated in a neurodegenerative disease. Overall design: RNA profiles in Striatum of WT and R6/1 mice by deep sequencing using Illumina HiSeq 2000.
Publication Title
Altered enhancer transcription underlies Huntington's disease striatal transcriptional signature.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from triplicate log-phase cultures of BY4741 (WT) transformed with pRS313-HA3-SSN6 and taf14D transformed with pRS313-HA3-SSN6 (empty vector), full-length pRS313-TAF14-HA3-SSN6, or pRS313-taf14W81A-HA3-SSN6 cultured in synthetic complete media lacking histidine. Overall design: Examination of changes in gene expression when the YEATS domain of Taf14 is mutated so it cannot bind acetyl-H3.
Publication Title
Association of Taf14 with acetylated histone H3 directs gene transcription and the DNA damage response.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Ion Torrent Proton
Description
The neurobiological functions of a number of kinases expressed in the brain are unknown. Here, we report new findings on DCLK3 (Doublecortin-like kinase 3) which is preferentially expressed in neurons in the striatum and dentate gyrus. Its function has never been investigated. DCLK3 expression is markedly reduced in Huntington''s disease. Recent data obtained in studies related to cancer suggest DCLK3 could have anti-apoptotic effect. Thus, we hypothesized that early loss of DCLK3 in Huntington''s disease may render striatal neurons more susceptible to mutant huntingtin (mHtt). We discovered that DCLK3 silencing in the striatum of mice exacerbated the toxicity of an N-terminal fragment of mHtt. Conversely, overexpression of DCLK3 reduced neurodegeneration produced by mHtt. DCLK3 also produced beneficial effects on motor symptoms in a knock-in mouse model of Huntington''s disease. Using different mutants of DCLK3, we found that the kinase activity of the protein plays a key role in neuroprotection. To investigate the potential mechanisms underlying DCLK3 effects, we studied the transcriptional changes produced by the kinase domain in human striatal neurons in culture. Results show that DCLK3 regulates in a kinase-dependent manner the expression of many genes involved in transcription regulation and nucleosome/chromatin remodeling. Consistent with this, histological evaluation showed DCLK3 is present in the nucleus of striatal neurons and, protein-protein interaction experiments suggested that the kinase domain interacts with zinc finger proteins, including TADA3, a core component of SAGA complex. Our novel findings suggest that the presence of DCLK3 in striatal neurons may play a key role in transcription regulation and chromatin remodeling in these brain cells, and show that reduced expression of the kinase in Huntington's disease could render the striatum highly vulnerable to neurodegeneration. Examination of DCLK3 as neuroprotector against mutant huntingtin in vivo and in vitro models. Overall design: Examination of DCLK3 as neuroprotector against mutant huntingtin in vitro experiments.
Publication Title
The striatal kinase DCLK3 produces neuroprotection against mutant huntingtin.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process of effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer. Results: Colony formation and sulforhodamine B (IC50 < 1nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a signature, termed rapamycin metagene index (RMI), of 31 genes upregulated by rapamycin treatment in vitro as well as in vivo (false discovery rate of 10%). In the Miller dataset, RMI was significantly associated with tumor size or lymph node status. High (>75) percentile) RMI was significantly associated with longer survival (P = 0.015). On multivariate analysis, RMI (P = 0.029), tumor size (P = 0.015) and lymph node status (P = 0.01) were prognostic. In van 't Veer study, RMI was not associated with the time to develop distant metastasis (P = 0.41). In Wang dataset, RMI predicted time to disease relapse (P = 0.09). Conclusions: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment. Mol Cancer. 2009 Sep 24;8(1):75.
Publication Title
The rapamycin-regulated gene expression signature determines prognosis for breast cancer.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 78 Downloadable Samples
- Illumina HiSeq 2500
Description
Post-traumatic stress disorder is a concerning psycho behavioral disorder thought to emerge from the complex interaction between genetic and environmental factors. For soldiers exposed to combat, the risk of developing this disorder is two-fold and diagnosis is often late, when much sequela has set in. To be able to identify and diagnose in advance those at “risk” of developing PTSD, would greatly taper the gap between late sequelae and treatment. Therefore, this study sought to test the hypothesis that the transcriptome can be used to track the development of PTSD in this unique and susceptible cohort of individuals. Gene expression levels in peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms) were determined by RNA sequencing technology following their return from deployment to Afghanistan. Count-based gene expression quantification, normalization and differential analysis (with thorough correction for confounders) revealed significant differences in two genes, LRP8 and GOLM1 . These preliminary results provide a proof-of-principle for the diagnostic utility of blood-based gene expression profiles for tracking symptoms of post-traumatic stress disorder in soldiers returning from tour. It is also the first to report transcriptome-wide expression profiles alongside a post-traumatic symptom checklist. Overall design: Peripheral blood samples from 85 Canadian infantry soldiers (n = 58 subjects negative for PTSD symptoms and n = 27 subjects with PTSD symptoms)
Publication Title
Using Next-Generation Sequencing Transcriptomics To Determine Markers of Post-traumatic Symptoms: Preliminary Findings from a Post-deployment Cohort of Soldiers.
Sample Metadata Fields
Sex, Subject
View Samples- Pseudomonas aeruginosa
- 6 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
Several bacterial human pathogens regulate the production of virulence factors by temperature, expressing them only at 37 C. Accordingly we show that the production of all P. aeruginosa virulence factors that are dependent on the QS transcriptional regulator RhlR, but only a fraction that are activated by LasR, are induced at 37 C compared to 30 C or 25 C. The RhlR-dependent induction at 37 C is a posttranscriptional effect due to an RNA thermometer of the ROSE family that thermoregulates the expression of rhlAB operon involved in rhamnolipids production, a virulence associated trait. This RNA structure also affects the expression of the downstream rhlR gene. A second thermometer is present upstream lasI and causes a reduced expression of this gene at lower temperatures without causing a significant decrease of the autoinducer 3-oxo-dodecanoyl homoserine lactone.
Publication Title
Regulation of Pseudomonas aeruginosa virulence factors by two novel RNA thermometers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 51 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Correlate the gene expression profiles with the most relevant patterns of chromosome abnormalities (cytogenetic subgroups of meningiomas) and the gene expression profiles could help to explain the differences in clinical behaviour of meningiomas.
Publication Title
Gene expression profiles of meningiomas are associated with tumor cytogenetics and patient outcome.
Sample Metadata Fields
Sex, Age, Disease stage
View Samples- Pseudomonas aeruginosa
- 12 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
The transcriptional regulator AmpR controls expression of the AmpC -lactamase in P. aeruginosa and other bacteria. Studies have demonstrated that in addition to regulating ampC expression, AmpR also regulates the expression of the sigma factor AlgT/U and the production of some quorum-sensing regulated virulence factors. In order to understand the ampR regulon, we compared the expression profiles of PAO1 and its isogenic ampR mutant, PAOampR in the presence and absence of sub-MIC -lactam stress. The analysis demonstrates that the ampR regulon is much more extensive than previously thought, with the deletion of ampR affecting the expression of over 300 genes. Expression of an additional 207 genes are affected by AmpR when the cells are exposed to sub-MIC -lactam stress, indicating that the ampR regulon in P. aeruginosa is much more extensive than previously thought.
Publication Title
The regulatory repertoire of Pseudomonas aeruginosa AmpC ß-lactamase regulator AmpR includes virulence genes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Time series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision.
Publication Title
Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 50 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The behavior of breast cancers and their response to neoadjuvant systemic therapy depend on their phenotype which is to a large extent determined by gene expression programs within the cancer cell.
Publication Title
Gene expression, molecular class changes, and pathway analysis after neoadjuvant systemic therapy for breast cancer.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples