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GSE55450
Mus musculus
20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Upstream Binding Factor (UBF) is a unique multi-HMGB-box protein first identified as a co-factor in RNA polymerase I (RPI/PolI) transcription. However, its poor DNA sequence selectivity and its ability to generate nucleosome-like nucleoprotein complexes suggest a more generalized role in chromatin structure. We previously showed that extensive depletion of UBF reduced the number of actively transcribed ribosomal RNA (rRNA) genes, but had little effect on rRNA synthesis rates or cell proliferation, leaving open the question of its requirement for RPI transcription. Using conditional gene deletion in mouse, we now show that UBF is indeed essential for transcription of the rRNA genes.
Publication Title
Conditional inactivation of Upstream Binding Factor reveals its epigenetic functions and the existence of a somatic nucleolar precursor body.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 2 Downloadable Samples
Illumina HiSeq 2000
Description
C/EBPa induces transdifferentiation of B cells into macrophages at high efficiencies and enhances reprogramming into induced pluripotent stem cells (iPSCs) when co-expressed with Oct4, Sox2, Klf4 and Myc (OSKM). However, how C/EBPa accomplishes these effects is unclear. We now found that transient C/EBPa expression followed by OSKM activation induces a 100 fold increase in iPSC reprogramming efficiency, involving 95% of the cells. During this conversion pluripotency and epithelial-mesenchymal transition genes become dramatically up-regulated and 60% of the cells express Oct4 within 2 days. C/EBPa acts as a pathbreaker since it transiently makes the chromatin of pluripotency genes more accessible to DNase I. It also induces the expression of the dioxygenase Tet2 and promotes its translocation to the nucleus where it binds to regulatory regions of pluripotency genes that become demethylated following OSKM induction. In line with these findings, overexpression of Tet2 enhances OSKM-induced B cell reprogramming. Since the enzyme is also required for efficient C/EBPa-induced immune cell conversion, our data suggest that Tet2 provides a mechanistic link between iPSC reprogramming and B cell transdifferentiation. The rapid iPS reprogramming approach described should help to fully elucidate the process and has potential clinical applications. Overall design: Change in gene expression, comparing primary B-cells treated with estradiol for 18h to induce C/EBPa to untreated cells.
Publication Title
Time-resolved gene expression profiling during reprogramming of C/EBPα-pulsed B cells into iPS cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 96 Downloadable Samples
- Illumina HiSeq 2500
Description
Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come primarily from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network. Overall design: mRNA expression profiling by RNA-seq of 10 tissues from wild-type (WT) and Cyrano–/– (CyrKO) mice. This study consists of 96 polyA-selected unstranded Tru-seq libraries prepared from 4–6 biological replicates per genotype for each tissue.
Publication Title
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2500
Description
Noncoding RNAs (ncRNAs) play increasingly appreciated gene-regulatory roles. Here, we describe a regulatory network centered on four ncRNAs—a long ncRNA, a circular RNA, and two microRNAs—using gene editing in mice to probe the molecular consequences of disrupting key components of this network. The long ncRNA Cyrano uses an extensively paired site to miR-7 to trigger destruction of this microRNA. Cyrano-directed miR-7 degradation is much more efficient than previously described examples of target-directed microRNA degradation, which come from studies of artificial and viral RNAs. By reducing miR-7 levels, Cyrano prevents repression of miR-7–targeted mRNAs and enables the accumulation of Cdr1as, a circular RNA known to regulate neuronal activity. Without Cyrano, excess miR-7 causes cytoplasmic destruction of Cdr1as, in part through enhanced slicing of Cdr1as by a second miRNA, miR-671. Thus, several types of ncRNAs can collaborate to establish a sophisticated regulatory network. Overall design: mRNA expression profiling by RNA-seq of cerebellum and cortex from wild-type (WT), Cyrano miR-7 site mutant (CyrMut), Cyrano–/– (CyrKO), and Mir7a1–/–; Mir7b–/– (Mir7DKO) mice. This study consists of 33 polyA-selected stranded NEXTflex libraries prepared from 3-4 biological replicates for each tissue and each genotype. To minimize batch effects, libraries for wild-type tissues were prepared and sequenced for each experiment and only intra-experiment comparisons were made.
Publication Title
A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 33 Downloadable Samples
- Illumina HiSeq 2000
Description
Recent studies have reported that competitive endogenous RNAs (ceRNAs) can act as sponges for a miRNA through their binding sites and that changes in ceRNA abundances from individual genes can modulate the miRNA’s activity. Consideration of this hypothesis would benefit from knowing the quantitative relationship between a miRNA and its endogenous target sites. Here, we altered intracellular target-site abundance through expression of a miR-122 target in hepatocytes and livers, and analyzed the effects on miR-122 target genes. Target repression was released in a threshold-like manner at high target-site abundance (=1.5x10^5 added target sites per cell), and this threshold was insensitive to the effective levels of the miRNA. Furthermore, in response to extreme metabolic liver disease models, global target-site abundance of hepatocytes did not change sufficiently to affect miRNA-mediated repression. Thus, modulation of miRNA target abundance is unlikely to cause significant effects on gene expression and metabolism through a ceRNA effect. Overall design: Seventeen mRNA profiles were generated of 1) primary hepatocytes of mice expressing variable levels of a recombinant Adenovirus expressing the transcript of AldolaseA (Ad-AldoA), containing either 1 or 3 sites matching miR-122 or a mutated miR-122 site (no site), 2) primary hepatocytes derived from mice treated with Antagomir-122 (treatment group) or Antagomir-122mm (control group), 3) livers originating of a genetic model (Ldlr deficient mice) causing severe pathological changes in cholesterol metabolism, 4) livers of mice perfused with Insulin or PBS, and 5) livers of mice fed a high-fat or chow diet; most samples were sequenced in duplicate or triplicate by an Illumina HiSeq 2000. One small RNA profile was also generated from livers of mice fed a chow diet by Solexa sequencing.
Publication Title
Assessing the ceRNA hypothesis with quantitative measurements of miRNA and target abundance.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tissue resident memory T cells (TRM) provide superior protection against infection localised to extra-lymphoid compartments in the body. Here we show that CD103+CD8+ TRM cells develop in skin from killer cell lectin-like receptor (KLR)G1-negative precursors that selectively infiltrate the epithelial layer. In the skin, a combination of chemokine-guided epithelial entry, local interleukin (IL)-15 and transforming growth factor (TGF)- signalling is required for formation and survival of these long-lived memory cells. Importantly, TRM differentiation results in the gradual acquisition of a unique transcriptional profile that differs from that expressed by memory cells in the circulation and other types of skin-resident intra-epithelial T cells, such as the dendritic epidermal T cells (DETC). We provide a comprehensive molecular and developmental framework for the local differentiation of a distinct type of peripheral memory T cell that contributes to an important first-line of immune defence in barrier tissues such as skin and mucosa.
Publication Title
The developmental pathway for CD103(+)CD8+ tissue-resident memory T cells of skin.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We used RNA-seq to compare the gene expression profiles of adult mouse prostate luminal cells and luminal cells that have the androgen receptor (AR) gene deleted. Our analyses show that AR-null luminal cells have altered expression levels of genes involved in cell-matrix adhesion, cytoskeleton regulation, and MAPK and TGF-beta signaling pathways. These results are consistent with our finding that AR-null luminal cells have abnormal cell morphology and loss of cell polarity. Overall design: Lineage marked wild-type luminal cells and AR-deleted luminal cells were flow-sorted based on YFP fluorescence respectively, and their expression profiles were analyzed by RNA-seq.
Publication Title
Dissecting cell-type-specific roles of androgen receptor in prostate homeostasis and regeneration through lineage tracing.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness.
Sample Metadata Fields
Sex, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Extensive loss of DNA methylation is a hallmark of cancer. The role of hypomethylation in altering gene expression in cancer cells has been poorly understood. Hepatic cellular carcinoma (HCC) is one of the most common human cancers. We use HCC as a model to investigate hypomethylation in cancer by a combination of methylated DNA immunoprecipitation and hybridization with comprehensive promoter arrays. We identify approximately 2,800 promoters that are hypomethylated in tumor samples. The hypomethylated promoters appear in clusters across the genome suggesting a high-level organization behind the epigenomic changes in cancer. The genes whose promoters are demethylated are mainly involved in cell growth, cell adhesion and communication, signal transduction, mobility and invasion; functions that are essential for cancer progression and metastasis. Previous studies suggested that MBD2 was involved in demethylation of uPA and MMP2 genes in human breast and prostate cancer cell lines. We extend these results here showing that whereas MBD2 depletion in normal liver cells has little or no effect, its depletion in the human hepatocellular carcinoma cell line HepG2 and the adenocarcinoma cell line SkHep1 results in suppression of cell growth, anchorage-independent growth and invasiveness, as well as an increase in promoter methylation and silencing of several of the genes that are hypomethylated in tumors. Our studies establish for the first time the rules governing hypomethylation of promoters in liver cancer and define the potential functional role of hypomethylation in cancer.
Publication Title
Definition of the landscape of promoter DNA hypomethylation in liver cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples