The Adar1 deaminase inactive mutant mouse tissue samples were obtain from the Walkley lab as described in http://www.ncbi.nlm.nih.gov/pubmed/26275108. We performed mmPCR-seq on the samples and measured the editing levels of. Overall design: Fetal mRNA profiles of E12.5 wild type (WT) and ADAR E861A mutant mice were generated by deep sequencing using Illumina HiSeq 2000.
Dynamic landscape and regulation of RNA editing in mammals.
Specimen part, Cell line, Subject
View SamplesWe examined if the minimal residual disease (MRD) and the Allelic Ratio (AR) of FLT3 internal tandem duplication (ITD) mutated patients may be prognostic factors. We correlated these parameters both with event free survival (EFS), with incidence of relapse and with gene expression profile (GEP). GEP showed that patients with high-ITD-AR or persistent MRD had different expression profiles. Results indicated that the ITD-AR levels and the MRD after I induction course are associated with transcriptional oncogenic profiles, which highlight differences in epigenetic control that may explain the variability in outcome among FLT3-ITD patients
Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.
Specimen part, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part, Subject
View SamplesEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2, TXK) in an independent cohort.
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease.
Sex, Age, Specimen part
View SamplesThe essential histone variant H2A.Z affects various DNA-based biological processes by so far not well understood mechanisms. Using a comprehensive label-free quantitative mass spectrometry-based approach we identified the human H2A.Z nucleosome interactome providing further insights into H2A.Z’s regulatory functions. Besides histone modification writer, eraser and reader complexes we identified PWWP2A as a novel H2A.Z-nucleosome binder. PWWP2A binds unprecedented strong to chromatin through a concerted multivalent binding mode. Two internal protein regions separately allow H2A.Z-specificity and nucleosome interaction, whereas the PWWP domain mediates direct DNA binding. PWWP2A is found at euchromatic regions where it preferable binds to the H2A.Z-nucleosome-containing transcriptional start sites of transcribed genes. Cellular depletion of PWWP2A results in impaired proliferation caused by a mitotic delay likely due to deregulation of involved target genes. According with the strong cellular phenotype, knockdown of frog PWWP2A leads to severe developmental cranial facial defects arising from neural crest cell differentiation and migration problems. Together, this study identifies PWWP2A as an H2A.Z-specific multivalent chromatin binder and provides a novel link between H2A.Z, chromosome segregation and organ development. Overall design: RNASeq of HeLa cells treated with control or PWWP siRNA
Multivalent binding of PWWP2A to H2A.Z regulates mitosis and neural crest differentiation.
No sample metadata fields
View SamplesNaive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are derived from the preimplantation epiblast and primordial germ cells (PGCs), respectively. We investigated whether differences exist between ESCs and EGCs, in view of their distinct developmental origins. PGCs are programmed to undergo global DNA demethylation; however, we find that EGCs and ESCs exhibit equivalent global DNA methylation levels. Importantly, inhibition of Erk and Gsk3b by 2i conditions leads to pronounced reduction in DNA methylation in both cell types. This is driven by Prdm14 and is associated with downregulation of Dnmt3a and Dnmt3b. However, genomic imprints are maintained in 2i, and we report derivation of EGCs with intact genomic imprints. Collectively, our findings establish that culture in 2i instills a naive pluripotent state with a distinctive epigenetic configuration that parallels molecular features observed in both the preimplantation epiblast and nascent PGCs.
Naive pluripotency is associated with global DNA hypomethylation.
Sex, Specimen part
View SamplesA congenic mouse line was constructed by introgressing a C3H chromosome 9 region harboring Ath29 into the C57BL/6 apoE-deficient background. RNA was extracted from aorta using a QIAGEN kit . Total RNA was pooled in an equal amount from 3 mice for each group. Standard Affymetrix procedures were performed using 8ug of total RNA.
Characterization of Ath29, a major mouse atherosclerosis susceptibility locus, and identification of Rcn2 as a novel regulator of cytokine expression.
Disease, Disease stage
View SamplesCoupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. The metamorphosis of the fruit fly represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, the mechanisms that coordinate development and immune cell activity in the transition from larva to adult in Drosophila remain to elucidate. The steroid hormone ecdysone is known to act as a key coordinator of metamorphosis. This hormone activates a nuclear receptor, the Ecdysone Receptor (EcR), which acts as a heterodimer with its partner Ultraspiracle (USP). Together, they activate the transcription of primary response genes, which in turn activate the transcription of a battery of late response genes. We have revealed that regulation of macrophage-like cells (hemocytes) by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. We have shown that in response to ecdysone signalling, hemocytes rapidly up regulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential to hemocyte immune functions and survival after infection.
Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Sex, Specimen part, Treatment
View SamplesAnalysis of skeletal muscle gene expression from type 2 diabetic volunteers before and after 16 weeks of chronic exercise training (two groups, one undergoing aerobic ecercise and the other resistance training exercise)
Multi-omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in Type 2 diabetic obesity.
Specimen part
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