SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq in six Smarcb1 deficient rhabdoid tumor cell lines, before and after Smarcb1 re-expression.
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.
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View SamplesSMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an epigenetic mechanism by which SMARCB1 loss drives transformation. Here, we show that despite indistinguishable mutational landscapes, human RTs show distinct enhancer H3K27ac signatures, which reveal remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared across all subtypes, such as SPRY1, and other lineage-specific super-enhancers like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based epigenetic mechanism underlying the tumor suppressive activity of SMARCB1. Overall design: RNA-seq for three primary Rhabdoid tumor samples
SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation.
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View SamplesThe objective of this study was to compare the transcriptional repertoire of mature human neutrophils before and after GM-CSF treatment by using oligonucleotide microarrays.
RhoH/TTF negatively regulates leukotriene production in neutrophils.
Specimen part
View SamplesThis dataset contains microarray data from normal controls (aged 20-99 yrs) and Alzheimer's disease cases, from 4 brain regions: hippocampus, entorhinal cortex, superior frontal cortex, post-central gyrus. Changes in expression of synaptic and immune related genes were analyzed, investigating age-related changes and AD-related changes, and region-specific patterns of change.
Gene expression changes in the course of normal brain aging are sexually dimorphic.
Sex, Subject
View SamplesThis dataset of cognitively normal controls is a subset of the GSE48350 dataset, which additionally contains microarray data from AD brains.
Gene expression changes in the course of normal brain aging are sexually dimorphic.
Sex, Subject
View SamplesPBMC from house dust mite (HDM) sensitized atopics with or without asthma (or nonallergic controls) were cultured in the presence or absence of HDM extract for 24 hours.
Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses.
Specimen part, Disease stage, Subject
View SamplesDNA methylation is essential for mammalian development and plays crucial roles in a variety of biological processes. The DNA methyltransferase Dnmt1 serves to maintain parental cell methylation patterns on daughter DNA strands in mitotic cells, however, the precise role of Dnmt1 in regulation of quiescent adult stem cells is not known.
DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells.
Specimen part
View SamplesIn order to find a relationship between gene expression of blood and brain in Rett Syndrome (RTT), we performed RNA sequencing on from cerebella and blood of 7 week-old male Mecp2-null mice (a model of RTT) and WT controls. Overall design: Transcriptional profiles were generated from cerebellum and blood of 3 Mecp2-null and 3 WT 7 week-old male mice, by RNAseq performed on an Illumina HiSeq 2000 System, generating approximately 60 million 2x75bp paired-end reads/sample. Blood and cerebellum samples originate from the same animal
Transcriptomic Analysis of <i>Mecp2</i> Mutant Mice Reveals Differentially Expressed Genes and Altered Mechanisms in Both Blood and Brain.
Age, Specimen part, Cell line, Subject
View SamplesWe sequenced mRNA extracted from heads of a D. melanogaster population that was sedated with a stream of ethanol saturated vapor, 30 minutes before RNA extraction; and from an age-matched untreated control group. Differential gene expression between the two groups was calculated and reported. Overall design: Examination of mRNA levels in heads of D. melanogaster adult females after ethanol exposure was performed using next generation sequencing (NGS) technology.
Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.
Cell line, Treatment, Subject
View SamplesVery little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen.
bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.
Time
View Samples