Epigenetic gene regulation in various oncogenic pathways is currently an important focus of cancer research. The PI3K pathway plays a pivotal role in hepatocellular carcinoma, but the significance of histone modification in the PI3K pathway-dependent hepatotumorigenesis remains unknown.
Impact of histone demethylase KDM3A-dependent AP-1 transactivity on hepatotumorigenesis induced by PI3K activation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesTo identify factors involved in tumorigenicity of glioma-initiating cells (GICs), we compared gene expression in GIC-like cells with and without sox11 expression.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part, Cell line
View SamplesTo identify factors involved in glioma-initiating cells (GICs), we compared gene expression between GIC-like cells and non-GICs.
Sox11 prevents tumorigenesis of glioma-initiating cells by inducing neuronal differentiation.
Specimen part
View SamplesHistone H3 lysine 9 (H3K9) methylation is an epigenetic mark of transcriptionally repressed chromatin. During mammalian development, H3K9 methylation levels seem to be spatiotemporally regulated by the opposing activities of methyltransferases and demethylases to govern correct gene expression. However, the combination(s) of H3K9 methyltransferase(s) and demethylase(s) that contribute to this regulation and the genes regulated by them remain unclear. Herein, we demonstrate the essential roles of H3K9 demethylases Jmjd1a and Jmjd1b in the embryogenesis and viability control of embryonic stem (ES) cells. Mouse embryos lacking Jmjd1a/Jmjd1b died after implantation. Depletion of Jmjd1a/Jmjd1b in mouse ES cells induced rapid cell death accompanied with a massive increase in H3K9 methylation. Jmjd1a/Jmjd1b depletion induced an increase in H3K9 methylation in the gene-rich regions of the chromosomes, indicating that Jmjd1a/Jmjd1b removes H3K9 methylation marks in the euchromatin. Importantly, the additional disruption of the H3K9 methyltransferase G9a in a Jmjd1a/Jmjd1b-deficient background rescued not only the H3K9 hypermethylation phenotype but also the cell death phenotype. We also found that Jmjd1a/Jmjd1b removes H3K9 methylation marks deposited by G9a in the Oct4 and Ccnd1 loci to activate transcription. In conclusion, Jmjd1a/Jmjd1b ensures ES cell viability by antagonizing G9a-mediated H3K9 hypermethylation in the gene-rich euchromatin.
Combined Loss of JMJD1A and JMJD1B Reveals Critical Roles for H3K9 Demethylation in the Maintenance of Embryonic Stem Cells and Early Embryogenesis.
Specimen part
View SamplesPulmonary dendritic cells are heterogenous cells comprise four distinct subsets including two conventional dendritic cell subsets, CD103+ and CD11bhiCD14lo cells, and two monocyte-derived dendritic cell subsets. Their functions in terms of migration and T cell activation are distinct, but genes regulating their features are to be determined.
Complement receptor C5aR1/CD88 and dipeptidyl peptidase-4/CD26 define distinct hematopoietic lineages of dendritic cells.
Sex, Specimen part
View SamplesActivation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes among others. We investigated the transcriptional regulation of the AID gene, Aicda, in the class switchinducible CH12F3-2 cells, and found that the Aicda regulation involves derepression by several layers of positive regulatory elements in addition to the 5 promoter region. The 5 upstream region contains functional motifs for the response to signaling by cytokines, CD40-ligand, or stimuli that activate NF-B. The first intron contains functional binding elements for the ubiquitous silencers c-Myb and E2f and for B cellspecific activator Pax5 and E-box-binding proteins.
B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
Specimen part
View SamplesTo clarify inflammatory genes whose expression is suppressed at high temperatures, we performed comprehensive analysis of gene expression by using a DNA microarray. Two independent primary cultures of mouse embryo fibroblasts (MEF1 and MEF2) were treated with LPS for 4 hours, or treated with LPS for 4 hours after the pretreatment with heat shock at 42C for 1 hour, and we identified 100 genes that undergo more than a 3-fold increase with LPS treatment. Remarkably, 86 genes (86%) underwent less than a 2-fold increase after combined treatments with heat shock and LPS in MEF1 and MEF2 cells.
Heat shock transcription factor 1 inhibits expression of IL-6 through activating transcription factor 3.
Specimen part
View SamplesInteraction of hematopoietic progenitors with the thymic stromal microenvironment induces them to proliferate, adopt the T cell fate, and asymmetrically diverge into multiple T lineages. Progenitors at various developmental stages are stratified among different regions of the thymus, implying that the corresponding microenvironments differ from one another, and provide unique sets of signals to progenitors migrating between them. The nature of these differences remains undefined. Here we use novel physical and computational approaches to characterize these stromal subregions, distinguishing gene expression in microdissected tissues from that of their lymphoid constituents. Using this approach, we comprehensively map gene expression in functionally distinct stromal microenvironments, and identify clusters of genes that define each region. Quite unexpectedly, we find that the central cortex lacks distinctive features of its own, and instead appears to function by sequestering unique microenvironments found at the cortical extremities, and modulating the relative proximity of progenitors moving between them.
Spatial mapping of thymic stromal microenvironments reveals unique features influencing T lymphoid differentiation.
Specimen part
View SamplesAnalysis of Foxp3(+)epigenetics(-) T cells, Foxp3(-)epigenetics(+) T cells, and Foxp3(+)epigenetics(+) T cells. Results indicate regulatory T cell (Treg) ontogenesis requires two independent processes, expression of the transcription factor Foxp3 and establishment of Treg epigenetic programs induced by T cell receptor (TCR) stimulation.
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
Specimen part
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