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SRP184505
Homo sapiens
22 Downloadable Samples
Illumina HiSeq 2500, NextSeq 550
Description
Transcriptional cofactors communicate regulatory cues from enhancers to promoters and are central effectors of transcription activation and gene expression, which is a hallmark of all multicellular organisms. However, the extent to which different cofactors display intrinsic specificity for distinct promoters is unclear. Testing intrinsic COF – core promoter (CP) compatibilities requires the systematic assessment of transcriptional activation for many CPs in the presence or absence of a given COF in an otherwise constant standardized reporter system. We therefore combined a plasmid-based high-throughput reporter assay, Self-Transcribing Active Core Promoter-sequencing (STAP-seq), with the specific recruitment of individual COFs to create a high-throughput activator bypass-like assay. Using this assay, we tested whether 5 different individually tethered human COFs (MED15, BRD4, EP300, MLL3 and EMSY) activate transcription from a selection of 12,000 candidate sequences encompassing different types of gene core promoters, enhancers and control sequences. In addition, we used the strong transcriptional activator P65 as a positive control and GFP as a negative control. We found that different COFs preferentially activate different CPs. For instance, MED15 prefers TATA-box containing CPs, while MLL3 preferentially activates CpG island promoters. The observed compatibilities between cofactors and promoters can explain how different enhancers specifically activate distinct sets of genes or alternative promoters within the same gene, and may underlie distinct transcriptional programs in human cells. Overall design: STAP-seq upon recruitment of individual transcriptional cofactor in HCT116 cells with 5 different cofactors and 2 controls, each in biological triplicate.
Publication Title
Transcriptional cofactors display specificity for distinct types of core promoters.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 39 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Medulloblastoma is the most frequent malignant pediatric brain tumor. Considerable efforts are dedicated to identify markers that help to refine treatment strategies. The activation of the Wnt/beta-catenin pathway occurs in 10-15% of medulloblastomas and has been recently described as a marker for favorable patient outcome. We report a series of 72 pediatric medulloblastomas evaluated for beta-catenin immunostaining, CTNNB1 mutations, and studied by comparative genomic hybridization. Gene expression profiles were also available in a subset of 40 cases. Immunostaining of beta-catenin showed extensive nuclear staining (>50% of the tumor cells) in 6 cases and focal nuclear staining (<10% of cells) in 3 cases. The other cases exhibited either a signal strictly limited to the cytoplasm (58 cases) or were negative (5 cases). CTNNB1 mutations were detected in all beta-catenin extensively nucleopositive cases. The expression profiles of these cases documented a strong activation of the Wnt/beta-catenin pathway. Remarkably, 5 out of these 6 tumors showed a complete loss of chromosome 6. In contrast, cases with focal nuclear beta-catenin staining, as well as tumors with negative or cytoplasmic staining, never demonstrated CTNNB1 mutation, Wnt/beta-catenin pathway activation or chromosome 6 loss. Patients with extensive nuclear staining were significantly older at diagnosis and were in continuous complete remission after a mean follow-up of 75.7 months (range 27.5-121.2) from diagnosis. All three patients with a focal nuclear staining of beta-catenin died within 36 months from diagnosis. Altogether, these data confirm and extend previous observations that CTNNB1-mutated tumors represent a distinct molecular subgroup of medulloblastomas with favorable outcome, indicating that therapy de-escalation should be considered. Yet, international consensus on the definition criteria of this distinct medulloblastoma subgroup should be achieved.
Publication Title
Beta-catenin status in paediatric medulloblastomas: correlation of immunohistochemical expression with mutational status, genetic profiles, and clinical characteristics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Pediatric medulloblastoma is considered a highly heterogeneous disease, and a new strategy of risk stratification to optimize therapeutic outcomes is required. We aimed to investigate a new risk-stratification approach based on expression profiles of medulloblastoma cohorts. We analyzed gene expression profiles of 30 primary medulloblastomas and detected strong evidence that poor survival outcome was significantly associated with mRNA expression profiles of 17p loss. However, it was not supported in independent cohorts from previously published data (n=100). We speculated that this controversy might come from complex conditions of two important prognostic determinants, loss of tumor suppressors (chromosome 17p) and high expression of oncogenes, c-myc (MYC) or N-myc (MYCN). Simultaneous consideration of these two factors led to a new subgrouping of patients, exhibiting obviously different survival expectancies between the subgroups. Patients with up-regulated WNT signalings were always pre-defined as an independent subgroup, which ultimately removed confounding effect arising from contradictory outcome, favorable prognosis of WNT medulloblastomas despite their high MYC/MYCN expression level. We also found that age is a significant prognostic marker after adjusting for 17p and MYC/MYCN status. Diminished survival in age <3 years was more substantial in groups with high expression of MYC/MYCN or 17p loss, indicating survival outcome might be coordinately affected by these three factors. We suggest a more tailored and easily applicable subgrouping system based on expression profiles of chromosome 17p and MYC/MYCN, while separating WNT medulloblastoma as an independent subgroup, which could provide the basis for a novel risk-stratification strategy in pediatric medulloblastoma.
Publication Title
Prognostic classification of pediatric medulloblastoma based on chromosome 17p loss, expression of MYCC and MYCN, and Wnt pathway activation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Expression profiling of resting B cells to classify active and silent genes based on expression levels Overall design: 4 biological replicates of mRNA extracted from freshly purified mouse CD43 negative resting B cells
Publication Title
The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
We used microarrays to compare gene expression between shRNA targeting NRL and control replicates in D458Med cell line.
Publication Title
NRL and CRX Define Photoreceptor Identity and Reveal Subgroup-Specific Dependencies in Medulloblastoma.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Comparison of expression of Arabidopsis thaliana Col-0 and T-DNA insertion line of RAP2.4a under time dependent light stress by transfer to high light
Publication Title
Meta-analysis of retrograde signaling in Arabidopsis thaliana reveals a core module of genes embedded in complex cellular signaling networks.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to imidazolinone (Arsenal) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
Publication Title
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered.
Publication Title
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to primisulfuron (Beacon) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
Publication Title
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to sulfometuron methyl (oust XP) herbicde that inhibits acetolactate synthase (ALS) enzyme and thus disrupts branmched chain amino acid biosynthesis. A number of genes related to amino acid, protein metabolism, growth, regulatory networks, respiratory pathways, stress, defense and secondary metabolism were altered.
Publication Title
A composite transcriptional signature differentiates responses towards closely related herbicides in Arabidopsis thaliana and Brassica napus.
Sample Metadata Fields
No sample metadata fields
View Samples