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SRP106243
Mus musculus
56 Downloadable Samples
Illumina HiSeq 2000
Description
Over-expression of the Myc transcription factor causes its widespread interaction with regulatory domains in the genome, but leads to the up- and down-regulation of discrete sets of genes. The molecular determinants of these selective transcriptional responses remain elusive. Here, we present an integrated time-course analysis of transcription and mRNA dynamics following Myc activation in proliferating mouse fibroblasts, based on chromatin immunoprecipitation, metabolic labeling of newly synthesized RNA, extensive sequencing and mathematical modeling. Transcriptional activation correlated with the highest increases in Myc binding at promoters. Repression followed a reciprocal scenario, with the lowest gains in Myc binding. Altogether, the relative abundance (henceforth, “share”) of Myc at promoters was the strongest predictor of transcriptional responses in diverse cell types, predominating over Myc's association with the co-repressor Miz1. Myc activation elicited immediate loading of RNAPII at activated promoters, followed by increases in pause-release5, while repressed promoters showed opposite effects. Gains and losses in RNAPII loading were proportional to the changes in the Myc share, suggesting that repression by Myc may be largely indirect, owing - at least in part - to competition for limiting amounts of RNAPII. Secondary to the changes in RNAPII loading, the dynamics of elongation and pre-mRNA processing were also rapidly altered at Myc regulated genes, leading to the transient accumulation of partially or aberrantly processed mRNAs. Altogether, our results shed light on how over-expressed Myc alters the various phases of the RNAPII cycle and the resulting transcriptional response. Overall design: Time course profiling of 4sU-labeled and total RNA upon Myc activation in 3T9-MycER mouse fibroblasts
Publication Title
Integrative analysis of RNA polymerase II and transcriptional dynamics upon MYC activation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Upon recruitment to active enhancers and promoters, RNA polymerase II (Pol_II) generates short non-coding transcripts of unclear function. The mechanisms that control the length and the amount of ncRNAs generated by cis-regulatory elements are largely unknown. Here, we show that the adapter protein WDR82 and its associated complexes actively limit such non-coding transcription. WDR82 targets the SET1/COMPASS H3K4 methyltransferase and the nuclear Protein Phosphatase 1 (PP1) complexes to the initiating Pol_II. WDR82 and PP1 also interact with components of the transcriptional termination and RNA processing machineries. Depletion of WDR82, SET1 or the PP1 subunit required for its nuclear import caused distinct but overlapping transcription termination defects at highly expressed genes, active enhancers and promoters, thus enabling the increased synthesis of unusually long ncRNAs. These data indicate that transcription initiated from cis-regulatory elements is tightly coordinated with termination mechanisms that impose the synthesis of short RNAs. Overall design: polyA-mRNAs or 4sU-labeled RNAs from BMDMs, either untreated or treated for with lipopolysaccharide (LPS) for the indicated time. Experiments were carried out in cells containing either a short hairpin targeting either of these: 1) Wdr82; 2) Set1a+Set1b; 3) Pnuts; or the empty vector (LMP) or a scrambled as a control. When specified, cells were pre-treated with 5,6-Dichloro-1-ß-D-ribofuranosylbenzimidazole (DRB) in order to prevent RNA polymerase II elongation.
Publication Title
Transcription of Mammalian cis-Regulatory Elements Is Restrained by Actively Enforced Early Termination.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Publication Title
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Role for naturally occurring CD4+CD25+Foxp3+ regulatory T cells (nTregs) in counterbalancing this process. Using a transgenic murine model for autoimmune-mediated lung disease, we demonstrated that, despite pulmonary inflammation, lung-specific CD8+ T cells can reside quiescently in close proximity to self-antigen. Whereas self-reactive CD8+ T cells in the inflamed lung and lung-draining lymph nodes down-regulated the expression of effector molecules, those located in the spleen appeared to be partly antigen-experienced and displayed a memory-like phenotype. Since ex vivo-reisolated self-reactive CD8+ T cells were very well capable to respond to the antigen in vitro, we investigated a possible contribution of nTregs to the immune control over autoaggressive CD8+ T cells in the lung.
Publication Title
CD4+CD25+Foxp3+ regulatory T cells are dispensable for controlling CD8+ T cell-mediated lung inflammation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
We performed genome-wide expression profiling of cells infected with control or RPS14 shRNAs.
Publication Title
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used an inducible ShRNA system and microarrays to detail the global programme of gene expression underlying neuroblastoma differentiation upon CHAF1A silencing .
Publication Title
Histone chaperone CHAF1A inhibits differentiation and promotes aggressive neuroblastoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of normal neuroblasts with malignant neuroblastomas (low- and high-stage)
Publication Title
Human fetal neuroblast and neuroblastoma transcriptome analysis confirms neuroblast origin and highlights neuroblastoma candidate genes.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In order to better understand chondrodysplasia disease mechanisms, we induced hypertrophic chondrocytes from chondrodysplasia-specific iPSCs and analyzed their gene expression profile.
Publication Title
Differentiation of Hypertrophic Chondrocytes from Human iPSCs for the In Vitro Modeling of Chondrodysplasias.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used microarrays to detail genome-wide gene expression underlying cardiac myocyte pathologies and identified candidate genes and specific pathways affecting cardiac myopathies
Publication Title
Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
JoMa1 cells are pluripotent precursor cells, derived from the neural crest of mice transgenic for tamoxifen-inducible c-Myc. Following transfection with a cDNA encoding for MYCN, cells become immortlized even in the absence of tamoxifen.
Publication Title
MYCN and ALKF1174L are sufficient to drive neuroblastoma development from neural crest progenitor cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples