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GSE46873
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Immuno-chemotherapy regimens elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumors in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that drives aggressive tumor growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma.
Publication Title
Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 1000
Description
Although the conserved AAA ATPase – bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2’s function as a facilitator of general chromatin-templated activities such as transcription. Overall design: We used a siRNA approach to knock-down Atad2 and measure the resulting variations in gene expression by RNA-seq
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Although the conserved AAA ATPase bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics and RNA-seq experiments in embryonic stem cells, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells, Atad2 becomes critical in sustaining specific gene expression programs, controlling proliferation and differentiation. Altogether, this work defines Atad2s function as a facilitator of general chromatin-templated activities such as transcription.
Publication Title
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 10 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Maize LEAFBLADELESS1 (LBL1) and Arabidopsis SUPPRESSOR OF GENE SILENCING3 (SGS3) play orthologous roles in the biogenesis of 21 nucleotide trans-acting short-interfering RNAs (tasiRNAs). The phenotypes conditioned by mutation of lbl1 and SGS3 are, however, strikingly different, suggesting that the activities of these small RNA biogenesis components, or the tasiRNAs and their targets might not be entirely conserved. To investigate the basis for this phenotypic variation, we compared the small RNA content between wild-type and lbl1 seedling apices. We show that LBL1 affects all major classes of small RNAs, and reveal unexpected crosstalk between tasiRNA biogenesis and other small RNA pathways regulating miRNAs, retrotransposons, and DNA transposons. We further identified genomic regions generating phased siRNAs, including numerous loci generating 22-nt phased small RNAs from long hairpin RNAs or overlapping antisense transcripts not previously described in other plant species. By combining both analyses, we identified nine TAS loci, all belonging to the conserved TAS3 family. Contrary to other plant species, no TAS loci targeted by a single miRNA were identified. Information from target prediction, RNAseq, and PARE analyses identified the tasiARFs as the major functional tasiRNAs in the maize vegetative apex where they regulate expression of ARF3 homologs. As such, divergence in TAS pathways is unlikely to account for the distinct phenotypes of tasiRNA biogenesis mutants in Arabidopsis and maize. Instead, the data suggests variation in the spatiotemporal regulation of ARF3, or divergence in its function, as a plausible basis for the dramatic phenotypic differences observed upon mutation of SGS3/lbl1 in Arabidopsis and maize. Overall design: An analysis of tasiRNA biogenesis, activity, and contribution to developmental phenotypes in the maize leaf. Data generated includes small RNA sequencing data and mRNA sequencing data. All data was generated in both wild type and lbl1 mutant maize leaf apices. Three replicates were generated for each genotype for the small RNA data. Two of these replicates were also used for the RNA-seq data.
Publication Title
Genome-wide analysis of leafbladeless1-regulated and phased small RNAs underscores the importance of the TAS3 ta-siRNA pathway to maize development.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Differential expression was used to access gene differences after Entamoeba histolytica infection.
Publication Title
The expression of REG 1A and REG 1B is increased during acute amebic colitis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this work, we isolated and characterized a novel cell population derived from human amniotic fluid cells (hAKPC-P), and we differentiated them into podocytes.
Publication Title
A novel source of cultured podocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The full complement of molecular pathways contributing to Parkinsons disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and -synuclein toxicity, we investigated a yeast model expressing -synuclein. Polyamines were found to enhance the toxicity of -synuclein, and an unbiased genome-wide screen for modifiers of -synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing -synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
Publication Title
Polyamine pathway contributes to the pathogenesis of Parkinson disease.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We found genetic deletion of IKK in mdx cardiomyocytes improved cardiac function and normalized calcium transients. We used microarrays to profile gene expression in hearts of mdx mice with intact IKK signaling and hearts of mdx mice with IKK-deficient cardiomyocytes to identify genes differentially regulated by NF-[kappa]B. signaling in dystrophic hearts.
Publication Title
NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model.
Sample Metadata Fields
Age
View Samples