This SuperSeries is composed of the SubSeries listed below.
A chromatin-modifying function of JNK during stem cell differentiation.
Specimen part, Treatment
View SamplesExpression profiling of from DMSO and SP600125 treated glutamatergic neurons reveals JNK target genes that are transcriptionally regulated by JNK signaling.
A chromatin-modifying function of JNK during stem cell differentiation.
Specimen part
View SamplesTo gain insights into the interplay between DNA methylation and gene regulation we generated a basepair resolution reference map of the mouse methylome in stem cells and neurons. High genome coverage allowed for a novel quantitative analysis of local methylation states, which identified Low Methylated Regions (LMR) with an average methylation of 30%. These regions are evolutionary conserved, reside outside of CpG islands and distal to promoters. They represent regulatory regions evidenced by their DNaseI hypersensitivity and chromatin marks of enhancer elements. LMRs are occupied by transcription factors (TF) and their reduced methylation requires TF binding while introduction of TF binding sites creates LMRs de novo. This dependency on TF activity is further evident when comparing the methylomes of embryonic stem cells and derived neuronal cells. LMRs present in both cell types are occupied by broadly expressed factors, while LMRs present at only one state are occupied by cell-type specific TFs. Methylome data can thus enhance the prediction of occupied TF binding sites and identification of active regulatory regions genome-wide. Our study provides reference methylomes for the mouse at two cell states, identifies a novel and highly dynamic feature of the epigenome that defines distal regulatory elements and shows that transcription factor binding dynamically shapes mammalian methylomes. Overall design: Strand specific expression profiling by high throughput sequencing.
DNA-binding factors shape the mouse methylome at distal regulatory regions.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.
Specimen part, Treatment
View SamplesExpression profiling of from Top2 knokout and ICRF-193 treated neurons reveals a significant number of genes that are transcriptionally deregulated
Target genes of Topoisomerase IIβ regulate neuronal survival and are defined by their chromatin state.
Specimen part, Treatment
View SamplesGlioblastomas (GBMs) are divided into CpG Island Methylator Phenotype (CIMP) and non-CIMP tumors. Non-CIMP GBMs derive from cells with non-disjunction of chromosome (chr7) and chromosome 10 (chr10), resulting in chr7 gain and chr10 loss, while CIMP GBMs have mutations in isocitrate dehydrogenase 1 or 2 (IDH1/2). Gain of chr7 is largely driven by PDGFA, but other genes on chr7 are likely to contribute to fitness gains and aggressiveness of these GBMs. We computationally investigated genes on chr7 whose gene expression correlated with survival, identifying HOXA5 as a potential driver of proneural gliomagenesis. Using a combination of human GBM cells and mouse PDGF-driven gliomas, we showed that HOXA5 drives increased proliferation and radiation resistance in culture and in vivo. These phenotypes appear to be in part due to effects on p53 and other apoptosis-related genes.
Increased <i>HOXA5</i> expression provides a selective advantage for gain of whole chromosome 7 in IDH wild-type glioblastoma.
Disease
View SamplesWe found that 5-Aza-dC/decitabine induces various prosurvival pathways (JAK-STAT-, NFkB-, MEK/ERK- and PI3K/AKTpathway) in cHL cell lines. Inhibition of these pathways with specific small molecular weight inhibitors potentiates the antitumor effect of 5-Aza-dC.
Activation of oncogenic pathways in classical Hodgkin lymphoma by decitabine: A rationale for combination with small molecular weight inhibitors.
Cell line
View SamplesKlotho-deficient mice develop aortic valve annulus calcification by 6 weeks of age. Understanding the molecular basis by which aortic valve calcification is initiated will help define potential molecular targets which may be inhibited to reduce or prevent aortic valve calcification.
COX2 inhibition reduces aortic valve calcification in vivo.
Specimen part
View SamplesAbstract.
The IKK2/NF-{kappa}B pathway suppresses MYC-induced lymphomagenesis.
Specimen part
View SamplesInnate immune responses of plant cells confer the first line of defence against pathogens. Signals generated by activated receptors are integrated inside the cell and converge on transcriptional programmes in the nucleus. The Arabidopsis Toll-related intracellular receptor RPS4 operates inside nuclei to trigger resistance to Pseudomonas bacteria expressing AvrRps4 and defence gene reprogramming through the stress response regulator, EDS1.
Arabidopsis TNL-WRKY domain receptor RRS1 contributes to temperature-conditioned RPS4 auto-immunity.
Specimen part
View Samples