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GSE15715
Mus musculus
2 Downloadable Samples
Description
Polycomb group (PcG) proteins control organism development by regulating the expression of developmental genes. Transcriptional regulation by PcG proteins is achieved at least partly through the PRC2-mediated methylation on lysine 27 of histone H3 (H3K27) and PRC1-mediated ubiquitylation on lysine 119 of histone H2A (uH2A). As an integral component of PRC1, Bmi1 has been demonstrated to be critical for H2A ubiquitylation. Although recent studies have revealed the genome wide binding patterns of some of the PRC1 and PRC2 components, as well as the H3K27me3 mark, there have been no reports describing genome wide localization of uH2A. Using the recently developed ChIP-Seq technology, here we report genome wide localization of the Bmi1-dependent uH2A mark in MEF cells. Gene promoter averaging analysis indicates a peak of uH2A just inside the transcription start site (TSS) of well annotated genes. This peak is enriched at promoters containing the H3K27me3 mark and represents the least expressed genes in WT MEF cells. In addition, peak finding reveals regions of local uH2A enrichment throughout the mouse genome, including almost 700 gene promoters. Genes with promoter peaks of uH2A exhibit lower level expression when compared to genes that do not contain promoter peaks of uH2A. Moreover, we demonstrate that genes with uH2A peaks have increased expression upon Bmi1 knockout. Importantly, local enrichment of uH2A is not limited to regions containing the H3K27me3 mark. We provide evidence to suggest that DNA methylation is tightly linked to H2A ubiquitylation in high density CpG promoters. Thus, our work not only reveals Bmi1-dependent H2A ubiquitylation but also suggests that uH2A targeting in differentiated cells may employ a different mechanism from that in ES cells.
Publication Title
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 2 Downloadable Samples
Description
Gene expression changes in mouse skeletal muscle were assessed in wild-type and Jhdm2a null skeletal muscle in an effort to define the role of Jhdm2a in energy expenditure and metabolism.
Publication Title
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Gallus gallus, Xenopus laevis, Mus musculus
- 20 Downloadable Samples
Description
One of the central issues in evolutionary developmental biology is how we can formulate the relationships between evolutionary and developmental processes. Two major models have been proposed: the 'funnel-like' model, in which the earliest embryo shows the most conserved morphological pattern, followed by diversifying later stages, and the 'hourglass' model, in which constraints are imposed to conserve organogenesis stages, which is called the phylotypic period. Here we perform a quantitative comparative transcriptome analysis of several model vertebrate embryos and show that the pharyngula stage is most conserved, whereas earlier and later stages are rather divergent. These results allow us to predict approximate developmental timetables between different species, and indicate that pharyngula embryos have the most conserved gene expression profiles, which may be the source of the basic body plan of vertebrates.
Publication Title
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 20 Downloadable Samples
Description
Transcription profiling of mouse development
Publication Title
Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Chronic obstructive pulmonary disease (COPD) is a heterogenous respiratory disease mainly caused by smoking. Respiratory infections constitute a major risk factor for acute worsening of COPD symptoms or COPD exacerbation. Mitochondrial functionality, which is crucial for the execution of physiologic functions of metabolically active cells, is impaired in airway epithelial cells (AECs) of COPD patients as well as smokers. However, the potential contribution of mitochondrial dysfunction in AECs to progression of COPD, infection-triggered exacerbations in AECs and a potential mechanistic link between mitochondrial and epithelial barrier dysfunction is unknown to date. In this study, we used an in vitro COPD exacerbation model based on AECs exposed to cigarette smoke extract (CSE) followed by infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress, as an indicator of mitochondrial stress were quantified upon CSE and Sp. The expression of proteins associated with mitophagy, mitochondrial content and biogenesis as well as mitochondrial fission and fusion was quantified upon CSE and Sp. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with mitochondrial function. We found that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp and may thus trigger COPD exacerbation.
Publication Title
Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Description
The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica (Bb) as the underlying model to comprehensively address effects on subsequent immune responses. Persistent carriage was associated with the stimulation of Bordetella-specific CD4+, CD8+ and CD4+CD25+Foxp3+ T cell responses and broad transcriptional activation was observed in CD4+CD25+ T cells. Importantly, transfer of lymphocytes from persistent carriers to acutely B. bronchiseptica infected mice resulted in a significantly increased bacterial burden in the recipients upper respiratory tract. In contrast, we found that B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. At the same time, vaccination and influenza A virus infection were unaffected. These data demonstrate that there are significant immune modulatory processes triggered by persistent B. bronchiseptica carriage that differentially affect subsequent immune responses. Thereby our results demonstrate the complexity of immune regulation induced by persistent bacterial carriage in the respiratory tract that can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 28 Downloadable Samples
Illumina HiSeq 1500
Description
There is evidence for the beneficial effect of FK506, an effective immunosuppressive agent, for the treatment of asthma however, the mechanisms underlying these effects are unclear. Using a mouse model of airway inflammation induced by Papain, a protease allergen, and RNAseq analysis of lung innate cells, we found that FK506 inhibited the activation of ILC2s, which initiate airway inflammation, as well as the induction of TH2 cells, which cause chronic inflammation. Our findings further support the clinical value of FK506 for the treatment of allergen-induced airway inflammation and clarify its targets and mechanisms of action. Overall design: Lung ILC2 cells, epithlial cells (type 1: AEC1 and type 2: AEC2), and basophils of mice were sorted and analyzed the transcriptome using Illumina HiSeq1500.
Publication Title
No associated publication
Sample Metadata Fields
Age, Specimen part, Genotype, Treatment, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
Description
Microarray experiments were performed using FAC-sorted young photoreceptors to analyze their transcriptome in comparison to remaining retinal cells at same developmental stage and retinal progenitors.
Publication Title
Increased integration of transplanted CD73-positive photoreceptor precursors into adult mouse retina.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
We aimed to define epithelial-specific genes in the kidney. In the developing mouse kidney at E12.5 epithelial cells are restricted to the ureteric bud, while mesenchymal cells surrounding the ureteric bud are non-epithelial. The mouse renal epithelial cell line mIMCD-3 was used to represent kidney epithelia in vitro. Gene expression was analyzed using Affymetrix microarrays in ureteric bud stalks, ureteric bud tips, and mIMCD-3 cells and compared to metanephric mesenchyme.
Publication Title
The transcription factor grainyhead-like 2 regulates the molecular composition of the epithelial apical junctional complex.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 24 Downloadable Samples
Description
Analysis of hematopoietic stem cells (HSC, LSK Flt3-) and myeloid progenitors (MP, LK CD34+) sorted from wildtype and Dnmt1 hypomorph mice
Publication Title
DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction.
Sample Metadata Fields
Specimen part
View Samples