Filters
Technology
Platform
SRP186159
Bos taurus
20 Downloadable Samples
Illumina HiSeq 3000
Description
We report the effect of DKK1 treatment during culture on the length and transcriptome of embryos on day 15 of development, supporting the notion that changes early in development affect later stages of development. Overall design: Bovine embryos were produced in vitro and exposed to either 0 or 100 ng/ml DKK1 from day 5 to 7 of culture. Embryos were transferred on day 7 and recovered on day 15 for evaluation of length and transciptome
Publication Title
Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Background & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy.
Publication Title
UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HiSeq 2000
Description
The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23. We show that di-acetylation at K5 and K8 of histone H4 (H4K5acK8ac) co-localizes with H3K27ac and BRD2 in the majority of active enhancers and promoters, where BRD2 has a stronger association with H4K5acK8ac than H3K27ac. Although BET inhibition by JQ1 led to complete reduction of BRD2 binding to chromatin, only local changes of H4K5acK8ac levels were observed, suggesting that recruitment of BRD2 does not influence global histone H4 hyperacetylation levels. This finding supports a model in which recruitment of BET proteins via histone H4 hyperacetylation is predominant over hyperacetylation of histone H4 by BET protein-associated acetyltransferases. In addition, we found a remarkable number of BRD2-bound genes, including MYC and its downstream target genes, were transcriptionally upregulated upon JQ1 treatment. Using BRD2-enriched sites and transcriptional activity analysis, we identified candidate transcription factors potentially involved in the JQ1 response in BRD2-dependent and independent manner. Overall design: Lung cancer cell line H23 was treated with JQ1 BET inhibitor. Gene expression profiling by CAGE was performed after 0h, 3h, 6h, 12h and 24h.
Publication Title
JQ1 affects BRD2-dependent and independent transcription regulation without disrupting H4-hyperacetylated chromatin states.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples GSE22176- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol and/or estrogen
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Oxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p
Publication Title
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000
Description
The juvenile onset of spermatogenesis in mice is analyzed by combining cytological and transcriptomic data in a novel computational analysis, resulting in meiotic substage-specific transcriptomes and the discovery of a transcription factor network that regulates the substages of meiosis. Overall design: Germ cells from testes of individual mice were obtained at two-day intervals from 8 to 18 days post-partum (dpp), with five biological replicates at each age (samples 8_1 through 18_5). Eight stages were discriminated cytologically by combinatorial antibody labeling, and RNA-seq was performed on the same samples. A novel permutation-based maximum covariance analysis (PMCA) method was developed to deconvolve genes into meiotic substages. To verify PMCA derived pachytene/diplotene substage-specific genes, we isolated enriched populations of adult pachytene germ cells (samples rep1 through rep4), followed the same RNA-seq protocol, and compared the PMCA derived substage-specific gene lists to the genes expressed in the pachytene/diplotene enriched germ cells.
Publication Title
Regulatory complexity revealed by integrated cytological and RNA-seq analyses of meiotic substages in mouse spermatocytes.
Sample Metadata Fields
Sex, Age, Cell line, Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina Genome Analyzer II
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Treatment
View Samples