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accession-icon GSE29297
Canonical NF-kB Activation is Essential for Epstein-Barr Virus Latent Membrane Protein 1 TES2/CTAR2 Gene Regulation.
  • organism-icon Homo sapiens
  • sample-icon 29 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Epstein-Barr Virus (EBV) Latent Membrane Protein 1 (LMP1) transforms rodent fibroblasts and is expressed in most EBV-associated malignancies. LMP1 Transformation Effector Site 2 (TES2)/C-Terminal Activation Region 2 (CTAR2) activates NF-kappaB, p38, JNK, ERK and IRF7 pathways. We have investigated LMP1 TES2 genome-wide RNA effects at 4 time points after LMP1 TES2 expression in HEK 293 cells. Using a False Discovery Rate (FDR) of < 0.001 after correction for multiple hypotheses, LMP1 TES2 caused > 2-fold changes in 1916 mRNAs; 1479 RNAs were up-regulated and 437 down-regulated. In contrast to TNFalpha stimulation, which transiently up-regulates many target genes, LMP1 TES2 maintained most RNA effects through the time course, despite robust and sustained induction of negative feedback regulators, such as IkappaBalpha and A20. LMP1 TES2 regulated RNAs encode many NF-kappaB signaling proteins and secondary interacting proteins. Consequently, many LMP1 TES2-regulated RNAs encode proteins that form an extensive interactome. Gene Set Enrichment Analyses found LMP1 TES2 up-regulated genes to be significantly enriched for Pathways in Cancer, B-and T-cell receptor signaling, and Toll-like receptor signaling. Surprisingly, LMP1 TES2 and IkappaBalpha super-repressor co-expression decreased LMP1 TES2 RNA effects to only 5 RNAs with FDR<0.001 and >2 fold change. Thus, canonical NF-kappaB activation is critical for almost all LMP1 TES2 RNA effects in HEK-293 cells and a more significant therapeutic target than previously appreciated.

Publication Title

Canonical NF-kappaB activation is essential for Epstein-Barr virus latent membrane protein 1 TES2/CTAR2 gene regulation.

Sample Metadata Fields

Specimen part

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accession-icon SRP096690
The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help
  • organism-icon Mus musculus
  • sample-icon 9 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1500

Description

Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch. Overall design: mRNA profiles of wild-type DZ, LZ, and Foxo1-deficient GC B cells were generated by deep sequencing in triplicate, using Illumina HiSeq 1500.

Publication Title

The transcription factor Foxo1 controls germinal center B cell proliferation in response to T cell help.

Sample Metadata Fields

Specimen part, Subject

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accession-icon SRP158979
Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nuceolin-AKT pathway.
  • organism-icon Homo sapiens
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

We found that CITED2 is highly expressed in metastatic prostate cancer, and its expression is correlated with poor survival in pateints. In this study, we used an siRNA to decrease CITED2 expression in PC3 cells. A RNA-seq approach was utilized in order to determine global gene expression changes in CITED2 knockdown cells compared to control cells. Overall design: PC3 cells transfected with control siRNAs were used as controls. Cells transfected with siRNAs targeting CITED2 were used as experimental group. Cells were transfected for 72 hr and the analyses were done.

Publication Title

Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE1407
HIV-based vector infected cells
  • organism-icon Homo sapiens
  • sample-icon 2 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U95 Version 2 Array (hgu95av2)

Description

SupT1, PBMC, or IMR90 cells were infected with an HIV-based vector (see Schroder et al., Cell 110:521-9) and the RNA isolated 48 hours after infection.

Publication Title

Retroviral DNA integration: ASLV, HIV, and MLV show distinct target site preferences.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP064469
Comparison of NP specific high and low affinity IgG1 Light zone GC B cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1500

Description

Despite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1 independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keeps Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of NP specific high and low affinity IgG1 LZ GC B cells were generated by deep sequencing using Illumina HiSeq 1500

Publication Title

Regulated selection of germinal-center cells into the memory B cell compartment.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon SRP068978
Comparison of Bach2-tdRFP high expression and low expression NP-specific IgG1 light zone GC B cells
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 1500

Description

Despite the importance of memory B cells for protection from recurrent infection, how these cells are selected during germinal center (GC) reactions remains unclear. We show here that light zone (LZ) GC B cells with lower affinity BCRs express a less CD40 signature and relatively high levels of Bach2, being prone to enter the memory B cell pool. We also find that Bach2 contributes to memory B cell generation in a Blimp-1-independent manner and that its higher expression confers on LZ GC cells a more advantage for entering the memory B cell compartment. Thus, our data support an instructive model in which weak T cell help keep Bach2 expression relatively high, thereby being predisposed to enter the memory pool. Overall design: mRNA expression profiles of Bach2-tdRFP low and high expression NP-specific IgG1 light zone GC B cells were generated by deep sequencing using Illumina HiSeq 1500.

Publication Title

Regulated selection of germinal-center cells into the memory B cell compartment.

Sample Metadata Fields

Specimen part, Subject

View Samples
accession-icon GSE24633
Cdx2 transcription factor binding in intestinal villus and gene expression profiling in Cdx mutant mice
  • organism-icon Mus musculus
  • sample-icon 11 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

We conditionally inactivated mouse Cdx2, a dominant regulator of intestinal development, and mapped its genome occupancy in adult intestinal villi. Although homeotic transformation, observed in Cdx2-null embryos, was absent in mutant adults, gene expression and cell morphology were vitally compromised. Lethality was accelerated in mice lacking both Cdx2 and its homolog Cdx1, with exaggeration of defects in crypt cell replication and enterocyte differentiation. Cdx2 occupancy correlated with hundreds of transcripts that fell but not with equal numbers that rose with Cdx loss, indicating a predominantly activating role at intestinal cis-regulatory regions. Integrated consideration of a mutant phenotype and cistrome hence reveals the continued and distinct requirement in adults of a master developmental regulator that activates tissue-specific genes.

Publication Title

Essential and redundant functions of caudal family proteins in activating adult intestinal genes.

Sample Metadata Fields

Specimen part

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accession-icon GSE7047
Transcriptome profile of Trypanosoma cruzi-infected cells
  • organism-icon Homo sapiens, Trypanosoma cruzi
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

As Trypanosoma cruzi, the etiological agent of Chagas disease, multiplies in the cytoplasm of nucleated host cells, infection with this parasite is highly likely to affect host cells. We performed an exhaustive transcriptome analysis of T. cruzi-infected HeLa cells using an oligonucleotide microarray containing probes for greater than 47,000 human gene transcripts. In comparison with uninfected cells, those infected with T. cruzi showed greater than threefold up-regulation of 41 genes and greater than threefold down-regulation of 23 genes. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) of selected, differentially expressed genes confirmed the microarray data. Many of these up- and down-regulated genes were related to cellular proliferation, including seven up-regulated genes encoding proliferation inhibitors and three down-regulated genes encoding proliferation promoters, strongly suggesting that T. cruzi infection inhibits host cell proliferation, which may allow more time for T. cruzi to replicate and produce its intracellular nests. These findings provide new insight into the molecular mechanisms by which intracellular T. cruzi infection influences the host cell, leading to pathogenicity.

Publication Title

Transcriptome profile of Trypanosoma cruzi-infected cells: simultaneous up- and down-regulation of proliferation inhibitors and promoters.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP032927
Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain (RNA-seq)
  • organism-icon Mus musculus
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

DNA methylation plays critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single-base resolution neuronal DNA methylome from the adult mouse dentate gyrus consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in low CpG-density regions, depleted at protein-DNA interaction sites, and anti-correlated with gene expression. Functionally, both mCpGs and mCpHs can repress transcription in vitro and are recognized by MeCP2 in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNMT3A for active maintenance in post-mitotic neurons. These characteristics of CpH methylation suggest a significantly expanded proportion of the neuronal genome under cytosine methylation regulation and provide a new framework for understanding the roles of this key epigenetic modification in neuronal identity, maturation, plasticity and neurological disorders. Overall design: Three biological replicates (dentate gyrus samples from C57Black6 mice) were analyzed by mRNA-seq

Publication Title

Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE40493
Bcl6-deficient regulatory T cells
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

gene expression data from wild-type and Bcl6-/- regulatory T cells

Publication Title

Bcl6 controls the Th2 inflammatory activity of regulatory T cells by repressing Gata3 function.

Sample Metadata Fields

Specimen part

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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