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GSE44644
Mus musculus
3 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The de novo DNA methyltransferase 3-like (Dnmt3L) is a catalytically inactive DNA methylase that has been previously shown to cooperate with Dnmt3a and Dnmt3b to methylate DNA. Dnmt3L is highly expressed in mouse embryonic stem cells (ESC) but its function in these cells is unknown. We here report that Dnmt3L is required for the differentiation of ESC into primordial germ cells (PGC) through activation of the homeotic gene Rhox5. By genome-wide analysis we found that Dnmt3L is a positive regulator of methylation at gene bodies of housekeeping genes and a negative regulator of methylation at promoters of bivalent genes. We demonstrate that Dnmt3L interacts with the Polycomb PRC2 complex in competition with the DNA methyl transferases Dnmt3a and Dnmt3b to maintain low the methylation level at H3H27me3 regions. Thus in ESC, Dnmt3L counteracts the activity of de novo DNA methylases to keep low the level of DNA methylation at developmental gene promoters.
Publication Title
Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA methylation at gene bodies in ESCs.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiScanSQ
Description
Ten eleven translocation (TET) enzymes catalyse the oxidative reactions of 5-methylcytosine (5mC) to promote the demethylation process. The reaction intermediate 5-hydroxymethylcytosine (5hmC) has been shown to be abundant in embryonic stem cells and tissues, but strongly depleted in human cancers. Genetic mutations of TET2 gene were associated with lleukemia, whereas TET1 downregulation has been shown to promote malignancy in breast cancer. Here, we report that TET1 is downregulated in colon tumours from the initial stage. TET1 silencing in primary epithelial colon cells increase their cellular proliferation while its re-expression in colon cancer cells inhibits their proliferation and the growth of tumour xenografts even at later stages. We found that TET1 binds and maintains hypomethylated the promoter of the DKK genes inhibitors of the WNT signalling to promote their expression. Downregulation of TET1 during colon cancer initiation leads to repression, by DNA methylation the promoters of the inhibitors of the WNT pathway resulting in a constitutive activation of the WNT pathway. Thus the DNA hydroxymethylation mediated by TET1 controlling the WNT signalling is a key player of tumour growth. These results provide new insights for understanding how tumours escape cellular controls Overall design: Transcriptome analysis of Caco-2 cell line expressing TET1 protein.
Publication Title
TET1 is a tumour suppressor that inhibits colon cancer growth by derepressing inhibitors of the WNT pathway.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We used microarrays to reveal the global expression profiles of young and old whole lateral ventricle choroid plexus tissue.
Publication Title
Age-Dependent Niche Signals from the Choroid Plexus Regulate Adult Neural Stem Cells.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
MicroRNAs are 19 to 23 nt RNAs that post-transcriptionally regulate gene expression. Human cells express several hundred miRNAs which regulate important biological pathways such as development, proliferation, and apoptosis. Recently, 12 microRNA genes have been identified within the genome of Kaposis sarcoma-associated herpesvirus; however, their functions are still unknown. To identify host cellular genes that may be targeted by these novel viral regulators, we performed gene expression profiling in cells stably expressing KSHV-encoded miRNAs. Data analysis revealed a set of 81 genes whose expression was significantly changed in the presence of miRNAs. While the majority of changes were below 2-fold, eight genes were down-regulated between 4- and 20-fold. We confirmed miRNA-dependent regulation for three of these genes and found that protein levels of thrombospondin 1 (THBS1) were decreased >10-fold. THBS1 has previously been reported to be down-regulated in KS lesions and has known activity as a strong tumor suppressor and anti-angiogenic factor, exerting its anti-angiogenic effect in part by activating the latent form of TGF-b. We show that reduced THBS1 expression in the presence of viral miRNAs translates into decreased TGF-b activity. These data suggest that KSHV-encoded miRNAs may contribute directly to pathogenesis by down-regulation of THBS1, a major regulator of cell adhesion, migration, and angiogenesis.
Publication Title
Identification of cellular genes targeted by KSHV-encoded microRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
RNA was purified from GFAP::GFP+CD133+ and GFAP::GFP+CD133+EGFR+ cells isolated from the adult mouse V-SVZ niche (GFAP::GFP mice, Jackson Mice Stock number 003257)
Publication Title
Prospective identification and purification of quiescent adult neural stem cells from their in vivo niche.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To more closely reproduce key cellular and stromal features of the desmoplastic reaction of cholangiocarcinoma in vitro, we developed a novel 3-dimensional culture modeling of cancer and stromal cells as a strategy for targeted therapies
Publication Title
Transforming Growth Factors α and β Are Essential for Modeling Cholangiocarcinoma Desmoplasia and Progression in a Three-Dimensional Organotypic Culture Model.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
TIMP-4 overexpression increases tumor burden in mice, promotes progenitor cell phenotype and sensitizes cells to apoptosis, by relying on NFkB signaling
Publication Title
Tissue inhibitor of metalloproteinases-4 (TIMP-4) regulates stemness in cervical cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Identifying target genes of the two human chromatin remodeling enzymes CHD3 and CHD4 Methods: see below in protocols Results: Libraries were sequenced on Illumina HiSeq2000 platform resulting in 37-71 Mio 50 bp paired-end reads per sample. We identified 16 (i) and 115 (ii) distinctly regulated genes when CHD3-GFP (i) or CHD4-GFP (ii) were overexpressed. Nine genes seem to be commonly regulated by CHD3 and CHD4. We successfully validated four genes from our RNA-seq via qPCR with two new (independent from those, used for RNA-seq) biological replicates. Conclusion: CHD3 and CHD4 regulate distinct genes. Overall design: Total RNA was prepared from 24 hours induced (1 ng/µl Dox) and non-induced Flp-In™ T-REx™ 293 cells, expressing GFP, hCHD3-GFP (UniProt: Q12873) or hCHD4-GFP(UniProt Q14839). Library preparation and Illumina Sequencing was perfprmed by EMBL GeneCore facility in Heidelberg (Germany: Dr. Vladimir Benes)
Publication Title
CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To investigate the mechanisms of PCa progression, we performed expression profiling of human prostate cancer and benign tissues.
Publication Title
Integration of tissue metabolomics, transcriptomics and immunohistochemistry reveals ERG- and gleason score-specific metabolomic alterations in prostate cancer.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples