We sequenced polyA mRNA from OVCAR8-ADR-Cas9 cells in which one or two of 3 epigenetic regulators (BRD4, KDM4C, KDM6B) had been knocked out to examine how global gene expression was affected and evaluate potential synergistic effects at a molecular level. Overall design: Gene expression data (RNA-Seq) in OVCAR8-ADR-Cas9 cells infected with control vector or vectors expressing gRNAs targeting one of 4 epigenetic regulators (BRD4, KDM4C, KDM6B) with biological replicates.
Multiplexed barcoded CRISPR-Cas9 screening enabled by CombiGEM.
No sample metadata fields
View SamplesBiological systems display extraordinary robustness. Robustness of transcriptional enhancers results mainly from clusters of binding sites for the same transcription factor, and it is not clear how robust enhancers can evolve loss of expression through point mutations. Here, we report the high-resolution functional dissection of a robust enhancer of the shavenbaby gene that has contributed to morphological evolution. We found that robustness is encoded by many binding sites for the transcriptional activator Arrowhead and that, during evolution, some of these activator sites were lost, weakening enhancer activity. Complete silencing of enhancer function, however, required evolution of a binding site for the spatially restricted potent repressor Abrupt. These findings illustrate that recruitment of repressor binding sites can overcome enhancer robustness and may minimize pleiotropic consequences of enhancer evolution. Recruitment of repression may be a general mode of evolution to break robust regulatory linkages. Overall design: 8 samples are analyzed: background GFP- and target GFP+ cells from four independent sortings.
Evolved Repression Overcomes Enhancer Robustness.
Specimen part, Subject
View SamplesThe goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Subject
View SamplesMicroarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.
Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: the potential impact of CXCL12/CXCR4 axis in EGFR<sub>mut</sub> NSCLC in diagnosis, follow-up and treatment.
No sample metadata fields
View SamplesMicroarray expression profiling was used to identify genes expressed misexpressed in wild-type Arabidopsis seedlings treated with 5-aza-2 deoxyctidine (5AC) or trichostatin A (TSA), and in decrease in dna methylation1 (ddm1) mutant seedlings.
Changes in global gene expression in response to chemical and genetic perturbation of chromatin structure.
Specimen part
View SamplesPdgfra-expressing (Pdgfra+) cells have been implicated as progenitors in many mesenchymal tissues. To further characterize Pdgfra+ cells during alveologensis, we performed single-cell RNA sequencing (scRNA-Seq) analysis using fluorescence-activated cell sorting (FACS) sorted GFP+ cells from Pdgfra-GFP lungs at P7 and P15. Overall design: We perfomed 10X genomics single-cell RNA-seq of Pdgfra-GFP+ cells at P7 and P15
<i>Pdgfra</i> marks a cellular lineage with distinct contributions to myofibroblasts in lung maturation and injury response.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
No sample metadata fields
View SamplesWe identified human-specific gene expression patterns in the brain by comparing expression with chimpanzee and rhesus macaque
Divergent whole-genome methylation maps of human and chimpanzee brains reveal epigenetic basis of human regulatory evolution.
No sample metadata fields
View SamplesGlucose is the most important metabolic substrate of the retina and maintenance of nor-moglycemia is an essential challenge for diabetic patients. Glycemic excursions could lead to cardiovascular disease, nephropathy, neuropathy and retinopathy. We recently showed that hy-poglycemia induced retinal cell death in mouse via caspase 3 activation and glutathione (GSH) decrease. Ex vivo experiments in 661W photoreceptor cells confirmed the low-glucose induction of death via superoxide production and activation of caspase 3, which was concomitant with a decrease of GSH content. We evaluate herein retinal gene expression 4 h and 48 h after insulin-induced hypoglycemia. Microarray analysis demonstrated clusters of genes whose expression is modified by hypoglycemia and we discuss the potential implication of those genes in retinal cell death. In addition, we highlight, by gene set enrichment analysis, three important pathways, including KEGG lysosomes, KEGG GSH metabolism and REACTOME apoptosis pathways. We tested the effect of recurrent hypoglycemia (three successive 5h periods of hypoglycemia separated by 48 h recovery) on retinal cell death. Interestingly, exposure to multiple hypoglycemic events prevents retinal cell death and GSH decrease, or adapts the retina to external stress by restoring GSH level comparable to control situation. We hypothesize that scavenger GSH is a key compound in this apoptotic process, and maintaining normal GSH level, as well as a strict glycemic control, may represent a therapeutic challenge in order to avoid side effects of diabetes, especially diabetic retinopathy.
Biological Characterization of Gene Response to Insulin-Induced Hypoglycemia in Mouse Retina.
Sex, Age, Specimen part
View SamplesThe H4K16 acetyltransferase MOF plays a crucial role in dosage compensation in Drosophila, but has additional, global functions in gene control. We compared the molecular context and effect of MOF activity in male and female flies combining chromosome-wide mapping and transcriptome studies with analyses of defined reporter loci in transgenic flies. MOF distributes dynamically between two types of complexes, the Dosage Compensation Complex (DCC) and complexes containing MBD-R2, a global facilitator of transcription. These different targeting principles define the distribution of MOF between the X chromosome and autosomes and at transcription units with 5 or 3 enrichment.
The activation potential of MOF is constrained for dosage compensation.
Cell line
View Samples