Influence of STIM1 on the transcriptome of CD4+ T cell subsets
STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
No sample metadata fields
View SamplesHow various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.
Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
No sample metadata fields
View SamplesHow various ATP-dependent chromatin remodellers bind to nucleosomes to regulate transcription is not well defined in mammalian cells. Here, we present genome-wide remodeller-interacting nucleosome profiles for Chd1, Chd2, Chd4, Chd6, Chd8, Chd9, Brg1 and Ep400 in mouse embryonic stem (ES) cells. These remodellers bind to nucleosomes at specific positions, either at one or both nucleosomes that flank each side of nucleosome-free promoter regions (NFRs), at enhancer elements, or within gene bodies. At promoters, bidirectional transcription commonly initiates on either side of remodeller-bound nucleosomes. Transcriptome analysis upon remodeller depletion reveals reciprocal mechanisms of transcriptional regulation by remodellers. At active genes, certain remodellers are positive regulators of transcription, whereas others act as repressors. At bivalent genes, which are bound by repressive Polycomb complexes, the same remodellers act in the opposite way. Together, these findings reveal how remodellers integrate promoter nucleosomal architecture to regulate ES cell transcription programs.
Genome-wide nucleosome specificity and function of chromatin remodellers in ES cells.
No sample metadata fields
View SamplesWe have analyzed the transcript expression in different LCM-dissected cell layers isolated from mouse retinas adapted to light or dark in order to identify transcripts potentially targetted by retinal microRNAs which are regulated in response to light treatment
Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs.
Specimen part, Treatment
View SamplesThe catalytic activities of covalent and ATP-dependent chromatin remodeling are central to regulating the conformational state of chromatin and the resultant transcriptional output. The enzymes that catalyze these activities are often contained within multiprotein complexes in nature. Two such multiprotein complexes, the polycomb repressive complex 2 (PRC2) methyltransferase and the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeler have been reported to act in opposition to each other during development and homeostasis. An imbalance in their activities induced by mutations/deletions in complex members (e.g. SMARCB1) has been suggested to be a pathogenic mechanism in certain human cancers. Here we show that preclinical models of synovial sarcoma - a cancer characterized by functional SMARCB1 loss via its displacement from the SWI/SNF complex through the pathognomonic SS18-SSX fusion protein - display sensitivity to pharmacologic inhibition of EZH2, the catalytic subunit of PRC2. Treatment with tazemetostat, a clinical-stage, selective and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity reverses a subset of synovial sarcoma gene expression and results in concentration-dependent cell growth inhibition and cell death specifically in SS18-SSX fusion-positive cells in vitro. Treatment of mice bearing either a cell line or two patient-derived xenograft models of synovial sarcoma leads to dose-dependent tumor growth inhibition with correlative inhibition of trimethylation levels of the EZH2-specific substrate, lysine 27 on histone H3. These data demonstrate a dependency of SS18-SSX-positive, SMARCB1-deficient synovial sarcomas on EZH2 enzymatic activity and suggests the potential utility of EZH2-targeted drugs in these genetically defined cancers. Overall design: Three different in vivo models of synovial sarcoma (xenograft: Fuji; PDX: CTG-0331 and CTG-0771) treated with or without the indicated dose of the EZH2 inhibitor, tazemetostat
Preclinical Evidence of Anti-Tumor Activity Induced by EZH2 Inhibition in Human Models of Synovial Sarcoma.
Subject
View SamplesEstrogen receptor- (ESR1) is an important transcriptional regulator in the mammalian oviduct, however ESR1-dependent regulation of this organ is not well defined, especially at the genomic level. The objective of this study was therefore to investigate estradiol- and ESR1-dependent regulation of the transcriptome of the oviduct using transgenic mice, both with (ESR1KO) and without (wild-type, WT) a global deletion of this transcription factor using the Affymetrix Genechip Mouse Genome 430-2.0 arrays.
Estrogen Receptor Alpha (ESR1)-Dependent Regulation of the Mouse Oviductal Transcriptome.
Sex, Specimen part, Treatment
View SamplesTo understand which genes acts downstream AtHB1 affecting hypocotyl growth in Arabidopsis thaliana, we performed transcriptional profiles of 4-day-old seedlings grown in a short-day regime comparing wild-type with athb1-1 mutant plants. These results show that some of the AtHB1-regulated genes modulate cell elongation, particularly cell wall composition and elongation, or encode proteins that serve as a source of carbon, nitrogen, and sulfur for early seedling growth. Overall design: RNA-Seq data for 4-day-old wild-type (Col-0) and athb1-1 mutant seedlings grown under short-day conditions. Biological triplicates were performed for each genotype analyzed.
Arabidopsis thaliana HomeoBox 1 (AtHB1), a Homedomain-Leucine Zipper I (HD-Zip I) transcription factor, is regulated by PHYTOCHROME-INTERACTING FACTOR 1 to promote hypocotyl elongation.
Subject
View SamplesWe used microarrays to investigate gene expression changes in healthy and leukemic cells from Pax5+/- and IL6+/-;Pax5+/- mice in CF and SPF housing conditions.
Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis.
Specimen part
View SamplesThe expression levels of Arabidopsis thaliana (Col-0) genes in several developmental stages during the seed-to-seedling transition were measured by using high-density Affymetrix arrays (Aragene.st1.1).
A Predictive Coexpression Network Identifies Novel Genes Controlling the Seed-to-Seedling Phase Transition in Arabidopsis thaliana.
No sample metadata fields
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