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Mus musculus
8 Downloadable Samples
Description
Cohesin, which consists of SMC1, SMC3, Rad21 and either SA1 or SA2, topologically embraces the chromatin fibers to hold sister chromatids together and to stabilize chromatin loops. Increasing evidence indicates that these loops are the organizing principle of higher-order chromatin architecture, which in turn is critical for gene expression. To determine how cohesin contributes to the establishment of tissue-specific transcriptional programs, we compared genome-wide cohesin distribution, gene expression and chromatin architecture in cerebral cortex and pancreas from adult mice. More than one third of cohesin binding sites differ between the two tissues and these are enriched at the regulatory regions of tissue-specific genes. Cohesin colocalizes extensively with the CCCTC-binding factor (CTCF). Cohesin/CTCF sites at active enhancers and promoters contain, at least, cohesin-SA1 whereas either cohesin-SA1 or cohesin-SA2 are present at active promoters independently of CTCF. Analyses of chromatin contacts at the Protocadherin gene cluster and the Regenerating islet-derived (Reg) gene cluster, mostly expressed in brain and pancreas respectively, revealed remarkable differences in the architecture of these loci in the two tissues that correlate with the presence of cohesin. Moreover, we found decreased binding of cohesin and reduced transcription of the Reg genes in the pancreas of SA1 heterozygous mice. Given that Reg proteins are involved in the control of inflammation in pancreas, such reduction may contribute to the increased incidence of pancreatic cancer reported in these animals. Overall design: Examination of the relationship between gene expression, genome wide cohesin distribution and chromatin structure
Publication Title
The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HiSeq 2000
Description
Changes in gene expression caused by CREBBP/EP300 bromodomain inhibitors in a CML cell line Overall design: K562 cells were treated with CBP30 and I-CBP112 and changes in gene expression were evaluated by RNA-seq
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
Cell line, Treatment, Subject
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SRP068961- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
Antiprolifereative effects of CREBBP/EP300 inhibitors were tested in human leukemia and lymphoma cell lines and the molecular mechanisms responsible for such effects were explored. Overall design: K562 cells were treated with CBP-30 (CREBBP/EP300 bromodomain inhibitor), C646 (CREBBP/EP300 HAT activity inhibitor) and JQ1 (BRD4 inhibitor) and changes in gene expression were evaluated by RNA-seq.
Publication Title
CREBBP/EP300 bromodomains are critical to sustain the GATA1/MYC regulatory axis in proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- IlluminaHiSeq2000
Description
The histone methyltransferase NSD2/WHSC1/MMSET is overexpressed in a number of solid tumors but its contribution to the biology of these tumors is not well understood. Here, we describe that NSD2 contributes to the proliferation of a subset of lung cancer cell lines by supporting oncogenic RAS transcriptional responses. Co-treatment with MEK and BRD4 inhibitors causes co-operative inhibitory responses on cell growth. While these inhibitors converge in the downregulation of genes associated with cancer-acquired super-enhancers, NSD2 inhibition complements their action by affecting the expression of clusters of genes embedded in megabase-scale regions marked with H3K36me2. Thus, combinatorial therapies using MEK or BRD4 inhibitors together with NSD2 inhibition ensure a more comprehensive inhibition of oncogenic RAS-driven transcription programs. Overall design: H1299 cells were transduced with doxycycline (dox) inducible shRNAs (sh3 or sh5) againts NSD2 and with non target shRNA (shNT). Changes in gene expression (RNA-seq) and H3K36me2 (ChIP-seq) caused by depletion of NSD2 and indicated treatments were assessed. Two replicates (Rep) for RNA-seq and three replicates for ChIP-seq were included.
Publication Title
NSD2 contributes to oncogenic RAS-driven transcription in lung cancer cells through long-range epigenetic activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
RNA-seq was performed using the RNA extracted from the bottom half of right lobe of mouse livers. Mice fall into two groups, mutant group which express ectopic hURI and their control littermates which do not express hURI. Two time points were considered in the study, 1-week-old mice, expressing hURI since 1 week (n =3, 4 for control and mutant, respectively) and 8-week-old mice expressing hURI since 8 week (n= 4, 3 for control and mutant, respectively), as hURI is expressed since conception. Overall design: Determination of differentially expressed transcripts over two time points (1 week and 8 weeks) in mouse livers expressing hURI (1 week and 8 weeks).
Publication Title
Inhibition of de novo NAD(+) synthesis by oncogenic URI causes liver tumorigenesis through DNA damage.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- NextSeq 500
Description
There is a growing body of evidence about the presence and the activity of the miRISC in the nucleus of mammalian cells. Here, we show by quantitative proteomic analysis that Ago2 interacts with nucleoplasmic Sfpq in a RNA-dependent fashion. By HITS-CLIP and transcriptomic analyses, we demonstrated that Sfpq directly controls the miRNA targeting of a subset of crucial miRNA-target mRNAs when it binds locally. Sfpq modulates miRNA targeting in both nucleoplasm and cytoplasm, indicating a nucleoplasmic imprinting of Sfpq-target mRNAs that influence miRNA targeting in both cellular compartments. Mechanistically, Sfpq binds to a sizeable set of long 3'UTR forming long aggregates to optimize miRNA position/recruitment to selected binding sites, as we show for Lin28A mRNA. These results extend the miRNA-mediated post-transcriptional gene silencing into the nucleoplasm and indicate that an unique Sfpq-dependent post-transcriptional strategy for controlling both nuclear and cytoplasmic gene expression takes place in cells during physio-pathological events. Overall design: RNA-seq of P19 cells control and upon SFPQ knockdown both in triplicates
Publication Title
Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.
Publication Title
The UBC-40 Urothelial Bladder Cancer cell line index: a genomic resource for functional studies.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Altered phosphatidylcholine (PC) metabolism in epithelial ovarian cancer (EOC) can provide choline-based imaging approaches as powerful tools to improve diagnosis and identify new therapeutic targets. Biochemical, protein and mRNA expression analyses demonstrated that the increase in the major choline-containing metabolite phosphocholine (PCho) in EOC compared with normal and non-tumoral immortalized counterparts (EONT) mainly rely upon: 1) ChoK activation, consistent with higher protein content and increased ChoKalpha mRNA expression levels; 2) PC-plc activation, consistent with higher, previously reported, protein expression. More limited and variable sources of PCho could derive, in some EOC cells, from activation of Phospholipase D or GPC-pd. Phospholipase A2 activity and isoforms expression levels were lower or unchanged in EOC compared with EONT cells. Increased ChoKalpha mRNA, as well as ChoK and PC-plc protein expression, were also detected in surgical specimens isolated from EOC patients. Overall, we demonstrated that the elevated PCho pool detected in EOC cells primarily resulted from the upregulation/activation of ChoK and PC-plc involved in the biosynthetic and in a degradative pathway of the PC-cycle, respectively.
Publication Title
Activation of phosphatidylcholine cycle enzymes in human epithelial ovarian cancer cells.
Sample Metadata Fields
Age, Specimen part, Disease stage, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Purpose: Asess the transcritpional changes induced upon RAB7 knock-down in melanoma (SK-Mel-28 and UACC-62) and in colon cancer (HCT-116) cell lines. Methods: mRNA profiles of tumor cell lines (SK-Mel-28, UACC-62, HCT-116) stably expressing scrambled shRNA or RAB7 shRNA (harvested at day 3 after lentiviral infection) were generated by deep sequencing, using three biological replicates per condition. The sequence reads that passed quality filters were analyzed with TopHat and Cufflinks. Validation of induced / silenced genes was performed by western blot. Results show a differential impact of RAB7 expression in the transcriptomic profile of melanoma vs non-melanoma cell lines, and support a lineage-specific role of this small GTPase in melanoma. Overall design: Examination of the mRNA profiles RAB7-depleted vs wild type cells, performed in parallel in 3 different tumor cell lines (Melanomas: SK-Mel-28 and UACC-62, Non-melanoma: HCT-116) harvested at day 3 after lentiviral infection.
Publication Title
RAB7 controls melanoma progression by exploiting a lineage-specific wiring of the endolysosomal pathway.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
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