Adaptation of C. elegans to hypertonic environments involves the accumulation of the organic osmolyte glycerol via transcriptional upregulation of the glycerol biosynthestic enzyme gpdh-1. A number of mutants, termed osmotic stress resistant (osr) mutants, have been identified. osr mutants cause constitutive upregulation of gpdh-1 and confer extreme resistance to hypertonicity. We tested the hypothesis that osr mutants broadly activate a gene expression program normally activated by osmotic stress in wild type animals using Affymterix microarray analysis of the hypertonic stress response in wild type animals and of constituitive gene expression changes in five osr mutants.
Genetic and physiological activation of osmosensitive gene expression mimics transcriptional signatures of pathogen infection in C. elegans.
Specimen part
View SamplesBackground: The prefrontal cortex is important in regulating sleep and mood. Diurnally regulated genes in the prefrontal cortex may be controlled by the circadian system, by the sleep-wake states, or by cellular metabolism or environmental responses. Bioinformatics analysis of these genes will provide insights into a wide-range of pathways that are involved in the pathophysiology of sleep disorders and psychiatric disorders with sleep disturbances. Results: We examined gene expression in the mouse prefrontal cortex at four time points during the 24-hour (12-hour light:12-hour dark) cycle by microarrays, and identified 3,890 transcripts corresponding to 2,927 genes with diurnally regulated expression patterns. We show that 16% of the genes identified in our study are orthologs of identified clock, clock controlled or sleep/wakefulness induced genes in the mouse liver and SCN, rat cortex and cerebellum, or Drosophila head. The diurnal expression patterns were confirmed in 16 out of 18 genes in an independent set of RNA samples. The diurnal genes fall into eight temporal categories with distinct functional attributes, as assessed by the Gene Ontology classification and by the analysis of enriched transcription factor binding sites. Conclusions: Our analysis demonstrates that ~10% of transcripts have diurnally regulated expression patterns in the mouse prefrontal cortex. Functional annotation of these genes will be important for the selection of candidate genes for behavioural mutants in the mouse and for genetic studies of disorders associated with anomalies in the sleep:wake cycle and circadian rhythms.
Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex.
No sample metadata fields
View SamplesHippocamus and amygdala expression was examined in nave, conditioned stimulus exposed, and fear conditioned mice 30 minutes after behavioral manipulation
Differential transcriptional response to nonassociative and associative components of classical fear conditioning in the amygdala and hippocampus.
No sample metadata fields
View SamplesSignal transduction from the extracellular matrix to the arterial wall plays a critical role during development of the vasculature. We now report the discovery of a Myocardin-like Protein (MKL)2/TGF- signaling pathway that is required for maturation and stabilization of the vasculature. Mkl2-/- null embryos exhibit profound derangements in the tunica media leading to aneurismal dilation, dissection and hemorrhage.
Myocardin-like protein 2 regulates TGFβ signaling in embryonic stem cells and the developing vasculature.
Specimen part
View SamplesLeft ventricular myocardium was snap-frozen at time of cardiac transplantation from patients with advanced idiopathic or ischemic cardiomyopathy, or at time of harvest from unused donor heart that serve as a nonfailing control. No subjects received mechanical support devices.
Transcriptional genomics associates FOX transcription factors with human heart failure.
No sample metadata fields
View SamplesCTCF is a multifunctional nuclear factor involved in epigenetic regulation. We have used transgenic RNA interference to deplete maternal stores of CTCF from growing mouse oocytes, and identified the potential target genes
Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development.
No sample metadata fields
View SamplesWe have utilized the RNA-Seq technology to identify genes with distinct expression patterns between failing and non-failing hearts. In an era of next-generation sequencing studies, our study demonstrates how knowledge gained from a small set of samples with accurately measured gene expressions using RNA-Seq can be leveraged as a complementary strategy to discern the genetics of complex disorders.
RNA-Seq identifies novel myocardial gene expression signatures of heart failure.
Sex, Age, Specimen part, Disease
View SamplesWe used microarrays to detail the global programme of gene expression underlying the effect of sleep deprivation in the mouse hippocampus and identified distinct classes of regulated genes during this process.
Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus.
Age, Specimen part, Treatment
View SamplesCTCF (CCCTC-binding factor) is a highly conserved 11-zinc finger DNA binding protein with tens of thousands of binding sites genome-wide. CTCF acts as a multifunctional regulator of transcription, having been previously associated with activator, repressor, and insulator activity. These diverse regulatory functions are crucial for preimplantation development and are implicated in the regulation of numerous lineage-specific genes. Despite playing a critical role in developmental gene regulation, the mechanisms that underlie developmental changes in CTCF recruitment and function are poorly understood. Our previous work suggested that differences in CTCF’s binding site sequence may affect the regulation of CTCF recruitment, as well as CTCF’s regulatory function. To investigate these two possibilities directly during a developmental process, changes in genome-wide CTCF binding and gene expression were characterized during in vitro differentiation of mouse embryonic stem cells. CTCF binding sites were initially separated into three classes (named LowOc, MedOc, and HighOc) based on similarity to the consensus motif. The LowOc class, with lower-similarity to the consensus motif, is more likely to show changes in binding during differentiation. These more dynamically bound sites are enriched for motifs that confer a lower in vitro affinity for CTCF, suggesting a mechanism where sites with low-binding affinity are more amenable to developmental control. Additionally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. In sum, these results suggest that the regulatory control of CTCF’s binding and function is dependent in part upon specific motifs within its DNA binding site. Overall design: Mouse E14 ES cells were differentiated in vitro for 4.5 days using retinoic acid. RNA-Seq was performed from cells collected before and after differentiation.
CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.
Cell line
View Samples