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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- Arabidopsis thaliana
- 8 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In seedlings, the induction of shade avoidance syndrome (SAS) involves a rapid up-regulation for known shade marker genes and subsequently activates an interacting network of various hormones that will eventually lead to cell elongation. We found that the B-box protein AtBBX24 have positive effects on the SAS (positive regulators). Global expression analysis of col and bbx24 seedlings reveals that a large number of genes involved in hormonal signaling pathways are positively regulated by BBX24 in response to simulated shade.
Publication Title
The transcriptional regulator BBX24 impairs DELLA activity to promote shade avoidance in Arabidopsis thaliana.
Sample Metadata Fields
Specimen part, Treatment
View Samples
GSE102137- Mus musculus
- 17 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression in FOXO KO vs WT brain
Publication Title
FOXO protects against age-progressive axonal degeneration.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To accelerate the development of disease-modifying therapeutics for Huntingtons disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed.
Publication Title
Transcriptional modulator H2A histone family, member Y (H2AFY) marks Huntington disease activity in man and mouse.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
AbstractFollicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses. Deficiency of mTORC2 impaired CD4+ T cell accumulation and IgA production, and aberrantly induced Foxo1 transcription factor. Mechanistically, the costimulatory molecule ICOS activated mTORC1 and mTORC2 to drive glycolysis and lipogenesis, and Glut1-mediated glucose metabolism promoted Tfh cell responses. Altogether, mTOR acts as a central node in Tfh cells to link immune signals to glucose metabolism and transcriptional activity.
Publication Title
mTORC1 and mTORC2 Kinase Signaling and Glucose Metabolism Drive Follicular Helper T Cell Differentiation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 3000
Description
Effector (Teff) and regulatory (Treg) CD4 T cells undergo metabolic reprogramming to support proliferation and immune function. While Phosphatidylinositide 3-kinase (PI3K)/Akt/mTORC1 signaling induces the glucose transporter Glut1 and aerobic glycolysis for Teff proliferation and inflammatory function, mechanisms that regulate Treg metabolism and function remain unclear. We show that TLR signals that promote Treg proliferation increase Glut1, PI3K/Akt/mTORC1 signaling, and glycolysis. However, TLR-induced mTORC1 signaling also impaired Treg suppressive capacity. Conversely, FoxP3 opposed PI3K/Akt/mTOR signaling to reduce glycolysis and anabolic metabolism while increasing oxidative and catabolic metabolism. Importantly, Glut1 expression was sufficient to increase Treg numbers but reduced suppressive capacity and FoxP3 expression. Thus, inflammatory signals and FoxP3 balance mTORC1 signaling and glucose metabolism to control Treg proliferation and suppressive function. Overall design: RNAseq of induced Glut1 transgenic and control Treg
Publication Title
Foxp3 and Toll-like receptor signaling balance T<sub>reg</sub> cell anabolic metabolism for suppression.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Sel1L is an adaptor protein for the E3 ligase Hrd1 involved in endoplasmic reticulum-associated degradation (ERAD). Its physiological importance in mammalian ERAD, however, remains to be established. Here, using the inducible Sel1L knockout mouse and cell models, we provide the first in vivo evidence that Sel1L is indispensable for Hrd1 stability, ER homeostasis and survival. Acute loss of Sel1L leads to premature death in adult mice within 3 weeks with profound pancreatic atrophy. Contrary to current belief, our data show that mammalian Sel1L is required for Hrd1 stability and ERAD function both in vitro and in vivo. Sel1L deficiency disturbs ER homeostasis, activates ER stress, attenuates translation and promotes cell death. Serendipitously, using biochemical approach coupled with mass spectrometry, we found that Sel1L deficiency causes the aggregation of both small and large ribosomal subunits. Thus, Sel1L is an indispensable component of mammalian ERAD and ER homeostasis, which is essential for protein translation, pancreatic function, cellular and organismal survival.
Publication Title
Sel1L is indispensable for mammalian endoplasmic reticulum-associated degradation, endoplasmic reticulum homeostasis, and survival.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Monocytes were induced to mature to macrophages with M-CSF. Cells were then activated with Interferon gamma and LPS or IL-4.
Publication Title
Transcriptional profiling of the human monocyte-to-macrophage differentiation and polarization: new molecules and patterns of gene expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Parkinsons disease (PD) progresses relentlessly and affects five million people worldwide. Laboratory tests for PD are critically needed for developing treatments designed to slow or prevent progression of the disease. We performed a transcriptome-wide scan in 105 individuals to interrogate the molecular processes perturbed in cellular blood of patients with early-stage PD. The molecular marker here identified is strongly associated with risk of PD in 66 samples of the training set (third tertile cross-validated odds ratio of 5.7 {P for trend 0.005}). It is further validated in 39 independent test samples (third tertile odds ratio of 5.1 {P for trend 0.04}). The genes differentially expressed in patients with PD, or Alzheimers or progressive supranuclear palsy offer unique insights into disease-linked processes detectable in peripheral blood. Combining gene expression scans in blood and linked clinical data will facilitate the rapid characterization of candidate biomarkers as demonstrated here with respect to PD.
Publication Title
Molecular markers of early Parkinson's disease based on gene expression in blood.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
To identify gene expression changes associated with treatment of EV that carry high levels of miR-105 (from MDA-MB-231 and MCF10A/miR-105 cells) in human breast tumor derived CAF, we analyzed RNA isolated from PBS- or EV-treated CAF. Gene expression in CAF treated with EV from MDA-MB-231 or MCF10A/miR-105 cells was compared to cells treated with PBS or EV from MCF10A cells, both of which served as controls in this experiment. Overall design: RNA was extracted from PBS- and EV-treated CAF, and subjected to library construction and RNA sequencing.
Publication Title
Cancer-cell-secreted exosomal miR-105 promotes tumour growth through the MYC-dependent metabolic reprogramming of stromal cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
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