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GSE79372
Homo sapiens
98 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 96 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance.
Publication Title
Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Oncogene-induced senescence (OIS) is a p53-dependent defence mechanism against uncontrolled proliferation. Consequently, many human tumours harbour p53 mutations while others show a dysfunctional p53 pathway, frequently by unknown mechanisms. We identified BRD7, a bromodomain-containing protein whose inhibition allows full neoplastic transformation in the presence of wild-type p53. Intriguingly, in human breast tumours harbouring wild-type, but not mutant p53, the BRD7 gene locus was frequently deleted and low BRD7 expression was found in a subgroup of tumours. Functionally, BRD7 is required for efficient p53-mediated transcription of a subset of target genes. BRD7 interacts with p53 and p300, and is recruited to target gene promoters, affecting histone acetylation, p53 acetylation, and promoter activity. Thus, BRD7 suppresses tumourigenicity by serving as a p53 cofactor required for efficient induction of p53-dependent OIS.
Publication Title
BRD7 is a candidate tumour suppressor gene required for p53 function.
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Purpose: Predominant causes of head and neck cancer recurrence after radiotherapy are rapid repopulation, hypoxia, fraction of cancer stem cells and intrinsic radioresistance. Currently, intrinsic radioresistance can only be assessed by ex-vivo colony assays. Besides being time-consuming, colony assays do not identify causes of intrinsic resistance. We aimed to identify a biomarker for intrinsic radioresistance to be used before start of treatment and to reveal biological processes that could be targeted to overcome intrinsic resistance.
Publication Title
Pretreatment microRNA Expression Impacting on Epithelial-to-Mesenchymal Transition Predicts Intrinsic Radiosensitivity in Head and Neck Cancer Cell Lines and Patients.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
Illumina Genome Analyzer II
Description
The local protein composition of chromatin is important for the regulation of transcription and other functions. By integrative analysis of genome-wide binding maps of 53 broadly selected chromatin components in Drosophila cells, we show that the genome is segmented into five principal chromatin types that are defined by unique, yet overlapping combinations of proteins, and form domains that can extend over >100 kb. We identify a novel repressive chromatin type that covers about half of the genome and lacks classic heterochromatin markers. Furthermore, transcriptionally active euchromatin consists of two distinct types that differ in molecular organization and H3K36 methylation, and regulate distinct classes of genes. Finally, we provide evidence that the different chromatin types act as guides that help to target DNA-binding factors to specific subsets of their recognition motifs. These results uncover basic principles of chromatin organization in a higher eukaryote. For this study, we generated whole-genome DamID binding profiles of 45 chromatin proteins in Drosophila Kc167 cells. Additionally, we perused published binding data of 8 chromatin proteins and generated a binding profile of one exogenous (yeast) DNA binding factor in Kc167 cells. On the same array platform, we obtained ChIP-on-chip profiles of histone H3, H1, H3K9me2, H3K27me3, H3K4me2, and H3K79me3. See supplementary files below. Gene expression was measured by RNA tag profiling. See GeneCounts supplementary file below. Overall design: [1] RNA tag sequences were optained on an Illumina GAII with the digital gene expression (DGE) module from duplicate RNA samples. [2] All DamID and ChIP experiments were done in Drosophila Kc167 cells in duplicate. Samples were hybridized to 380k NimbleGen arrays with 300 bp probe spacing. Every experiment was done in duplicate in the reverse dye orientation, where Dam-fusion material was hybridized over Dam-only material. For ChIP, immunoprecipitated material was hybridized over ChIP input material. 18 previously-submitted Samples were included in this study. 10 of 18 Samples have been renormalized for the GSE22069 study: GSM509087, GSM509088, GSM509089, GSM509090, GSM509091, GSM509092, GSM509093, GSM509094, GSM509095, GSM509096 New GSM accession numbers have been issued for these 10 samples. 8 of 18 Samples are identical in the original studies and in GSE22069: GSM423290, GSM423291, GSM423298, GSM423299, GSM493592, GSM493593, GSM509085, GSM509086 [3] The genomic locations in files GSE22069_norm_aggregated_discretized_tiling_arrays.txt and GSE22069_norm_aggregated_tiling_arrays.txt are relative to FlyBase release 5 (BDGP R5/dm3).
Publication Title
Systematic protein location mapping reveals five principal chromatin types in Drosophila cells.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Cell line, Treatment, Time
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
One major class of anti-cancer drugs targets topoisomerase II to induce DNA double-strand breaks and cell death of fast growing cells. In vitro experiments showed that doxorubicin can induce histone eviction as well as DNA damage, while etoposide can only induce DNA damage. Here, we compare the transcription responses of different tissues to doxorubicin or etoposide treatment in vivo.
Publication Title
Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically. Overall design: The effect of CDK6 knockdown and palbociclib treatment on SCCOHT cells.
Publication Title
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The PUF family of RNA binding proteins has a conserved role in maintaining stem cell self-renewal. FBF is a C. elegans PUF that is required to maintain germline stem cells (GSCs). To understand how FBF controls GSCs, we sought to identify is target mRNAs. Briefly, we immunoprecipitated FBF-mRNA complexes from worm extracts and then used microarrays to identify the FBF-associated mRNAs. To focus on germline targets of FBF, we used a FBF-GFP transgene under the control of a germline promoter and we used an anti-GFP antibody to purify FBF-GFP from worm extracts. In parallel, we also processed a strain expressing TUBULIN-GFP in the germline to control for mRNAs that non-specifically co-purify with GFP. We found that FBF associates with >1,000 unique mRNAs and likely controls a broad network of key cellular and developmental regulators.
Publication Title
Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
Publication Title
The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples