Illumina expression microarray analysis of TCam-2, 2102EP, NCCIT, JAR, MPAF, ARZ and FS1 cells 8 and 16 h after 10 nanomolar romidepsin application. DMSO treated cells were used as controls. These data are part of the article 'A signaling cascade including ARID1A, GADD45B and DUSP1 induces apoptosis and affects the cell cycle of germ cell cancers after romidepsin treatment' (Nettersheim et al., 2016).
A signaling cascade including ARID1A, GADD45B and DUSP1 induces apoptosis and affects the cell cycle of germ cell cancers after romidepsin treatment.
Cell line
View SamplesIllumina expression microarray analysis of shRNA-mediated PRAME knock down TCam-2 cells with and without all trans retinoic acid (ATRA) treatment for 8 days, of TCam-2 cells with and without ATRA (8d) and of in vitro cultivated GCC cell lines TCam-2, 2102EP, NCCIT and JAR. These data are part of the article 'The Cancer / Testis-Antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas'.
The cancer/testis-antigen PRAME supports the pluripotency network and represses somatic and germ cell differentiation programs in seminomas.
Specimen part, Cell line
View SamplesType II testicular germ cell cancers (GCC) are the most frequently diagnosed tumors in young men (20 - 40 years) and are classified as seminoma or non-seminoma. GCCs are commonly treated by orchiectomy and chemo- or radiotherapy. However, a subset of metastatic non-seminomas display only incomplete remission or relapse and require novel treatment options. Recent studies have shown effective application of the small-molecule inhibitor JQ1 in tumor therapy, which interferes with the function of bromodomain and extra-terminal (BET)-proteins. Here, we demonstrate that upon JQ1 doses 250 nM GCC cell lines and Sertoli cells display compromised survival and induction of cell cycle arrest. JQ1 treated GCC cell lines display upregulation of genes indicative for DNA damage and a cellular stress response. Additionally, downregulation of pluripotency factors and induction of mesodermal differentiation was detected. GCCs xenografted in vivo showed a reduction in tumor size, proliferation and angiogenesis when subjected to JQ1 treatment. The combination of JQ1 and the histone deacetylase inhibitor romidepsin further enhanced the apoptotic effect in vitro and in vivo. Thus, we propose that JQ1 alone, or in combination with romidepsin may serve as a novel therapeutic option for GCCs.
The bromodomain inhibitor JQ1 triggers growth arrest and apoptosis in testicular germ cell tumours in vitro and in vivo.
Specimen part, Cell line, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part, Cell line
View SamplesThe Ikaros zink finger transcription factor is a critical regulator of the hematopietic system, and plays an important role in the regulation of the development and function of several blood cell lineages.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Specimen part
View SamplesWe used microarrays to analyze gene expression changes in the Ikaros null ILC87 T cell tumor line after re-expression of Ikaros.
Ikaros mediates gene silencing in T cells through Polycomb repressive complex 2.
Cell line
View SamplesWe have used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. High throughput RNA-sequencing using a Nano-CAGE protocol throughout early embryogenesis revealed that the expression of repetitive elements is abundant in embryonic cells, highly dynamic and stage-specific, with most repetitive elements becoming repressed before implantation. Furthermore, we show that Line L1 elements and IAP retrotransposons become reactivated from both parental genomes in mouse embryos after fertilisation, indicating an open chromatin configuration at the beginning of development. Our data show that the reprogramming process that follows fertilisation is accompanied by a robust transcriptional activation of retrotransposons and suggests that expression of repetitive elements is initially regulated through an RNA-dependent mechanism in mammals. Overall design: Genome Wide profiling of CAGE transcripts using Nano-CAGE and RNAseq in oocytes and 3 different stages of mouse pre-implantation development
Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.
Age, Specimen part, Cell line, Subject
View SamplesThe methyl-cytosine binding protein 2 (MeCP2) is a reader of epigenetic DNA methylation marks and necessary and sufficient to reorganize 3D heterochromatin structure during cellular differentiation, e.g., myogenesis. In addition to global expression profile changes, myogenic differentiation is accompanied by 3D-heterochromatin reorganization that is dependent on MeCP2. MeCP2 is enriched at pericentric heterochromatin foci (chromocenters). During myogenesis, the total heterochromatin foci number per nucleus decreases while foci volumes and MeCP2 protein levels increase. Ectopic MeCP2 is able to mimic similar heterochromatin restructuring in the absence of differentiation.
Gene repositioning within the cell nucleus is not random and is determined by its genomic neighborhood.
Specimen part, Cell line
View SamplesTRIM24 and TRIM33 interact to form a corepressor complex that suppresses murine hepatocellular carcinoma (HCC). TRIM24 and TRIM33 cooperatively repress retinoic acid receptor dependent activity of VL30 retro-transposons in hepatocytes in vivo. In TRIM24 knockout hepatocytes, VL30 long terminal repeats (LTRs) generate enhancer (e)RNAs and act as surrogate promoter and enhancer elements deregulating expression of neighbouring genes. We show that a VL30 LTR-derived eRNA is essential to activate the lipocalin 13 gene in hepatocytes in vivo. A further consequence of VL30 de-repression is the accumulation of retro-transcribed VL30 DNA in the cytoplasm of TRIM24-mutant hepatocytes and activation of the viral defence/interferon response. VL30 activation therefore modulates gene expression via the enhancer activity of the LTRs and by activation of the interferon response. Both of these processes are genetically linked to HCC development suggesting that VL30 repression by TRIM24 plays an important role in tumour suppression. Overall design: RNA profiles in liver of wild type (WT) and Trim24-/- mice by deep sequencing using Illumina GAIIx.
Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA.
Age, Specimen part, Cell line, Subject
View SamplesDNA methylation is an essential epigenetic modification, present in both unique DNA sequences and repetitive elements, but its exact function in repetitive elements remains obscure. Here, we describe the genome-wide comparative analysis of the 5mC, 5hmC, 5fC and 5caC profiles of repetitive elements in mouse embryonic fibroblasts and mouse embryonic stem cells. We provide evidence for distinct and highly specific DNA methylation/oxidation patterns of the repetitive elements in both cell types, which mainly affect CA repeats and evolutionary conserved mouse-specific transposable elements including IAP-LTRs, SINEs B1m/B2m and L1Md-LINEs. DNA methylation controls the expression of these retro-elements, which are clustered at specific locations in the mouse genome. We show that TDG is implicated in the regulation of their unique DNA methylation/oxidation signatures and their dynamics. Our data suggest the existence of novel epigenetic code for the most recently acquired evolutionary conserved repeats that could play a major role in cell differentiation. Overall design: Transcriptome (RNA-seq) analyses of shRNA treated MEFs (control, shSCR or Tdg knockdown, shTDG).
Combinatorial DNA methylation codes at repetitive elements.
Cell line, Treatment, Subject
View Samples