H3.3 phosphorylation promotes high levels of histone acetylation in mouse embryonic stem cells, which are central to the initiation of new transcription during lineage specification. Overall design: RNA-Seq analysis in mouse embryonic stem cells (Control, H3.3KO, HIRAKO, ATRXKO, DAXXKO) and embryoid bodies at Day 4 of differentiation (Control and H3.3KO).
Phosphorylation of histone H3.3 at serine 31 promotes p300 activity and enhancer acetylation.
Specimen part, Cell line, Subject
View SamplesHeart failure is associated with high morbidity and mortality and its incidence increases worldwide. MicroRNAs (miRNAs) are potential markers and targets for diagnostic and therapeutic applications, respectively. We determined myocardial and circulating miRNA abundance and its changes in patients with stable and end-stage heart failure before and at different time points after mechanical unloading by a left ventricular assist device (LVAD) by small-RNA-sequencing. MiRNA changes in failing heart tissues partially resembled that of fetal myocardium. Consistent with prototypical miRNA–target-mRNA interactions, target mRNA levels were negatively correlated to changes in abundance for highly expressed miRNAs in heart failure and fetal hearts. The circulating small RNA profile was dominated by miRNAs, and fragments of tRNAs and small cytoplasmic RNAs. Heart- and muscle-specific circulating miRNAs (myomirs) increased up to 140-fold in advanced heart failure, which coincided with a similar increase in cardiac troponin I protein, the established marker for heart injury. These extracellular changes nearly completely reversed 3 months following initiation of LVAD support. In stable heart failure, circulating miRNAs showed less than 5-fold differences compared to normal, and myomir and cardiac troponin I levels were only captured near the detection limit. These findings provide the underpinning for miRNA-based therapies and emphasize the usefulness of circulating miRNAs as biomarkers for heart injury performing similar to established diagnostic protein biomarkers. Overall design: Total RNA isolated from human left ventricular myocardium of failing hearts due to dilated or ischemic cardiomyopathy before and after mechanical unloading by a left ventricular assist device, and fetal myocardium compared to non-failing postnatal myocardium was subjected to multiplexed small RNA-sequencing on the Illumina platform. mRNA gene expression data using Illumina HumanHT-12v4 beadarrays for a subset of the myocardial samples is available (GSE52601).
Comparative RNA-sequencing analysis of myocardial and circulating small RNAs in human heart failure and their utility as biomarkers.
No sample metadata fields
View SamplesWe compared the transcriptional profile of mammary tumors spontaneously developed in PyMT transgenic mice either bearing or not additional copies of the endogeneous SIRT6 gene.
SIRT6 Suppresses Cancer Stem-like Capacity in Tumors with PI3K Activation Independently of Its Deacetylase Activity.
Sex, Age, Specimen part
View SamplesmiR-92 enhances c-Myc induced apoptosis. In the R26MER/MER mouse embryonic fibroblasts (MEFs), a switchable variant of Myc, MycERT2, was knocked into the genomic region downstream of the constitutive Rosa26 promoter, allowing acute activation of c-Myc by 4-OHT-induced nuclear translocation. This in vitro system nicely recapitulates c-Myc-induced apoptosis, as activated MycERT2 induces strong p53-dependent apoptosis in response to serum starvation. Enforced miR-92 expression in three independent R26MER/MER MEF lines significantly enhanced Myc-induced apoptosis.
A component of the mir-17-92 polycistronic oncomir promotes oncogene-dependent apoptosis.
Specimen part
View SamplesRoberts syndrome (RBS) is a human developmental disorder caused by mutations in the cohesin acetyltransferase ESCO2. We previously reported that mTORC1 was inhibited and overall translation was reduced in RBS cells. Treatment of RBS cells with L-leucine partially rescued mTOR function and protein synthesis, correlating with increased cell division. In this study, we use RBS as a model for mTOR inhibition and analyze transcription and translation with ribosome profiling to determine genome-wide effects of L-leucine. The translational efficiency of many genes is increased with Lleucine in RBS cells including genes involved in ribosome biogenesis, translation, and mitochondrial function. snoRNAs are strongly upregulated in RBS cells, but decreased with L-leucine. Imprinted genes, including H19 and GTL2, are differentially expressed in RBS cells consistent with contribution to mTORC1 control. This study reveals dramatic effects of L-leucine stimulation of mTORC1 and supports that ESCO2 function is required for normal gene expression and translation. Overall design: 42 samples of human fibroblast cell lines with various genotypes (wt, corrected, and esco2 mutants) are treated with l-leucine or d-leucine (control) for 3 or 24 hours. Biological replicates are present.
Improved transcription and translation with L-leucine stimulation of mTORC1 in Roberts syndrome.
No sample metadata fields
View SamplesWe profiled and quantitated miRNAs in two skin tumors (Basal cell carcinoma and Merkel cell carcinoma) and identified tumor-specific miRNAs. We used these tumor-specific miRNAs to guide development of miRNA fluorescence in situ hybridization. Overall design: 2 barcoded sequencing runs, including 40 unique samples (36 used in manuscript). The details of each sample can be found in Supplementary Tables S1 and S2.
Multicolor microRNA FISH effectively differentiates tumor types.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesBACKGROUND & AIMS: We performed an integrated analysis to identify microRNAs (miRNAs) and mRNAs with altered expression in liver tumors from 3 mouse models of hepatocellular carcinoma (HCC) and human tumor tissues.
microRNA 193a-5p Regulates Levels of Nucleolar- and Spindle-Associated Protein 1 to Suppress Hepatocarcinogenesis.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View SamplesTo gain a more depth knowledge of repressive epigenetic gene regulation in UCC, we have profiled H3K9m3 and H3K27m3 in normal and malignant urothelial cells. We matched these profiles to those 5-methylcytosine and gene expression. We hypothesized that differences represent pro-carcinogenic events within the urothelium.
Integrated epigenome profiling of repressive histone modifications, DNA methylation and gene expression in normal and malignant urothelial cells.
Specimen part, Cell line
View Samples