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SRP069861
Mus musculus
26 Downloadable Samples
Illumina HiSeq 1500
Description
Genetic ablation of the maintenance methyltransferase Dnmt1 induces widespread demethylation and transcriptional activation of CpG-rich IAP (intracisternal A particle) proviruses. Here, we report that this phenomenon is not simply a consequence of loss of DNA methylation. By exploiting conditional deletions of Dnmt1 and Np95, each of which is essential for maintenance methylation, we find that while IAPs are indeed de-repressed in Dnmt1-ablated embryos and embryonic stem cells (ESCs), these proviruses remain silenced in Np95-ablated cells, despite similar kinetics of passive demethylation. Paradoxically, transient IAP activation in Dnmt1-ablated ESCs requires the presence of NP95. We subsequently show that in the absence of NP95, the H3K9 methyltransferase SETDB1 maintains IAP silencing; while in the absence of DNMT1, prolonged binding of NP95 to hemimethylated DNA perturbs SETDB1-dependent H3K9me3 deposition. Taken together, these observations reveal that following acute loss of Dnmt1, H3K9 methylation-dependent IAP silencing is disrupted by aberrant NP95 binding to hemimethylated DNA. Overall design: RNA-seq for Np95, Dnmt1 and Setdb1 wt, single conditional KO (cKO) and double cKO ES cells; RRBS-seq for Dnmt1 and Np95 single and double cKO ESCs; Myc-tagged NP95, DNMT1 ChIP-seq; and wt and Np95wt and cKO H3K9me3 ChIP-seq.
Publication Title
Activation of Endogenous Retroviruses in Dnmt1(-/-) ESCs Involves Disruption of SETDB1-Mediated Repression by NP95 Binding to Hemimethylated DNA.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- IonTorrentProton
Description
Tumor-specific alternative splicing is implicated in the progression of cancer, including clear cell renal cell carcinoma (ccRCC). Using ccRCC RNA-sequencing data from The Cancer Genome Atlas, we found that epithelial splicing regulatory protein 2 (ESRP2), one of the key regulators of alternative splicing in epithelial cells, is expressed in ccRCC. ESRP2 mRNA expression did not correlate with the overall survival rate of ccRCC patients, but the expression of some ESRP-target exons correlated with the good prognosis and with the expression of Arkadia (also known as RNF111) in ccRCC. Arkadia physically interacted with ESRP2, induced polyubiquitination, and modulated its splicing function. Arkadia and ESRP2 suppressed ccRCC tumor growth in a coordinated manner. Lower expression of Arkadia correlated with advanced tumor stages and poor outcomes in ccRCC patients. This study thus reveals a novel tumor-suppressive role of the Arkadia-ESRP2 axis in ccRCC. Overall design: Expression of mRNA in a ccRCC cell line OS-RC-2 under the knockdown of Arkadia or ESRP2. Knock-down of ESRP2 was confirmed by RT-PCR because of low expression of ESRP2 which resulted in non-quantitative FPKM value.
Publication Title
The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- IonTorrentProton
Description
We evaluated the role of Arkadia and ESRP2 in HEK293T cells Overall design: Expression of mRNA in HEK293T cells under the knockdown of Arkadia or ESRP2
Publication Title
The Arkadia-ESRP2 axis suppresses tumor progression: analyses in clear-cell renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smad2/3 are transcription factors that engage in TGF-beta-induced transcription. We determined and analyzed HepG2 and Hep3B-specific Smad2/3 binding sites by ChIP-chip. We used expression microarrays to compare the Smad2/3 and HNF4alpha binding sites identified by ChIP-chip or ChIP-seq, respectively, to TGF-beta-induced gene expressions.
Publication Title
Cell type-specific target selection by combinatorial binding of Smad2/3 proteins and hepatocyte nuclear factor 4alpha in HepG2 cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Experiment design
Publication Title
Glucose-dependent cell size is regulated by a G protein-coupled receptor system in yeast Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Preimplantation embryos undergo a transient wave of genome-wide demethylation with the exception of imprinted genes that are critical for fetal development. Here we show that the derivation of female mouse embryonic stem cells (ESCs) in the presence of inhibitors of MEK1/2 and Gsk3 (2i-ESCs), known as 2i or ground-state culture conditions, results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. In this study, we analyzed global gene expression profile and global DNA methylation status in 2i-ESCs and 2i-ESCs derived differentiated cells. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.
Publication Title
Derivation of ground-state female ES cells maintaining gamete-derived DNA methylation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interaction of ICOS - ICOS ligand is required for the germinal center formation, T-cell immune responses, and development of autoimmune diseases. Human ICOS deficiency with the identical ICOS mutation has been identified in nine patients worldwide. In vitro studies showed T-cell defect of the patients was mild, and in vivo autoimmunity was uncommon and mild. Here we report in-depth analysis of T-cell function in two siblings with novel ICOS deficiency. While the brother displayed mild skin infections, psoriasis-like skin region, and defective immunoglobulin class switching, the sister had more severe symptoms, which included immunodeficiency, rheumatoid arthritis, inflammatory bowel disease, interstitial pneumonitis, and psoriasis. Despite of normal CD3/CD28-induced proliferation and IL-2 production in vitro, peripheral blood T-cells from both patients demonstrated decreased percentage of CD4 central and effector memory T-cells and impaired production of Th1, Th2, and Th17 cytokines upon CD3/CD28 costimulation or upon PMA/ionophore stimulation. The defective polarization into effector cells were associated with impaired induction of T-bet, GATA3 and MAF and RORC. Reduced CTLA-4+CD45RO+ FoxP3+ regulatory T-cells and diminished induction of inhibitory cell surface molecules including CTLA-4 were also observed in the patients. Further analysis of the gene expression and immune functions of the patients demonstrated increased induction of RANKL, lack of IFN-g response, and loss of Itch expression upon activation in the female case with autoimmunity. Our study suggests extensive T-cell dysfunction and loss of balance between effector cells and regulatory cells in the ICOS-deficient patients may account for their immunodeficiency and/or autoimmune disorder.
Publication Title
Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The spontaneous pulmonary metastasis model of human uterine sarcoma was established using GFP-expressed MES-SA cells. Several sublines with different metastatic potentials were generated by in vivo passaging.
Publication Title
Establishment and characterization of a novel orthotopic mouse model for human uterine sarcoma with different metastatic potentials.
Sample Metadata Fields
Sex, Specimen part
View Samples