This SuperSeries is composed of the SubSeries listed below.
Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Treatment
View SamplesIn response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by TP63 in normal stratifying epithelia to maintain proliferative capacity or drive proliferation of squamous cell carcinomas, where TP63 is frequently overexpressed/amplified. Here we use ChIP-sequencing, integrated with microarray analysis, to define the genome wide interplay between TP53 and TP63 in response to genotoxic stress in normal cells. We reveal that TP53 and TP63 bind to overlapping, but distinct cistromes of sites through utilization of distinctive consensus motifs and that TP53 is constitutively bound to a number of sites. We demonstrate that cisplatin and adriamycin elicit distinct effects on TP53 and TP63 binding events, through which TP53 can induce or repress transcription of an extensive network of genes by direct binding and/or modulation of TP63 activity. Collectively, this results in a global TP53 dependent repression of cell cycle progression, mitosis and DNA damage repair concomitant with activation of anti-proliferative and pro-apoptotic canonical target genes. Further analyses reveals that in the absence of genotoxic stress TP63 plays an important role in maintaining expression of DNA repair genes, loss of which results in defective repair
Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
Treatment
View SamplesThis analysis identified 27 genes that are induced, and 29 that are repressed, by a factor of two or more in Asr1RING mutant cells. Genes in each category did not cluster according to gene ontology or chromosome, but we did notice that 33% of genes in the induced set lie within 50 kb of a telomere. In contrast, for repressed genes, only 7% were similarly telomere-proximal. The induction of subtelomeric gene expression in Asr1RING mutant cells suggests that the Ub-ligase activity of Asr1 may be required for authentic patterns of subtelomeric gene silencing. Overall design: Transcriptome of WT and Asr1 RING mutant cells grown at log phase in enriched media.
Antagonistic roles for the ubiquitin ligase Asr1 and the ubiquitin-specific protease Ubp3 in subtelomeric gene silencing.
Subject
View SamplesGenetic variation modulating risk of sporadic Parkinson's disease (PD) has been primarily explored through genome wide association studies (GWAS). However, like many other common genetic diseases, the impacted genes remain largely unknown. Here, we used single-cell RNA-seq to characterize dopaminergic (DA) neuron populations in the mouse brain at embryonic and early postnatal timepoints. These data facilitated unbiased identification of DA neuron subpopulations through their unique transcriptional profiles, including a novel postnatal neuroblast population and substantia nigra (SN) DA neurons. We use these population-specific data to develop a scoring system to prioritize candidate genes in all 49 GWAS intervals implicated in PD risk, including known PD genes and many with extensive supporting literature. As proof of principle, we confirm that the nigrostriatal pathway is compromised in Cplx1 null mice. Ultimately, this systematic approach establishes biologically pertinent candidates and testable hypotheses for sporadic PD, informing a new era of PD genetic research. Overall design: 473 single cell RNA-Seq samples from sorted mouse Th-eGFP+ dopaminergic neurons collected at two timepoints from three distinct brain regions.
Single-Cell RNA-Seq of Mouse Dopaminergic Neurons Informs Candidate Gene Selection for Sporadic Parkinson Disease.
Specimen part, Subject
View SamplesThe goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-nave iP and P.NP rats.
Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats.
Specimen part
View SamplesA highly significant quantitative trait locus (QTL) that influenced alcohol preference was identified in the iP/iNP rats on chromosome 4.
Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains.
No sample metadata fields
View SamplesThe simultaneous genotyping of tens of thousands of SNP using SNP microarrays is a very important tool that is revolutionizing genetics and molecular biology. In this work, we present a new application of this technique by using it to assess chromatin immunoprecipitation (CHIP) as a means to assess the multiple genomic locations bound by a protein complex recognized by an antibody. We illustrate the use of this technique with an analysis of the change in histone H4 acetylation, a marker of open chromatin and transcriptionally active genomic regions, which occur during the differentiation of human myoblasts into myotubes. Our results are validated by the observation of a significant correlation between the histone modifications detected and the expression of the nearby genes, as measured by DNA microarrays.
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
No sample metadata fields
View SamplesGene expression was determined for both myotubes and myoblasts using Affymetrix HG-U133 A/B arrays.
ChIP on SNP-chip for genome-wide analysis of human histone H4 hyperacetylation.
No sample metadata fields
View SamplesInfection is a major complication and cause of mortality and morbidity after acute stroke however the mechanisms are poorly understood. After experimental stroke the microarchitecture and cellular composition of the spleen are extensively disrupted resulting in deficits to immune function.
Experimental Stroke Differentially Affects Discrete Subpopulations of Splenic Macrophages.
Specimen part, Treatment
View SamplesRNA-seq with male and female juvenile and adult spinal cords Overall design: RNA was isolated from 4 week and 8 week spinal cords for sequencing
Age and Sex-Related Changes to Gene Expression in the Mouse Spinal Cord.
Sex, Age, Specimen part, Cell line, Subject
View Samples