Purpose: we tested the hypothesis that Hltf deletion in placenta either caused or exacerbated neonatal hypoglycemia via Hif-1a regulation of nutrient transporters. Methods: Individual samples [1 term placenta/sample x 5 biological replicates for test and control littermate female mice = 10 total samples] were flash frozen and sent to Otogenetics Corp. (Norcross, GA) for RNA-seq assays. Paired-end 100 nucleotide reads were aligned to genomic assembly mm10 and analyzed using the platform provided by DNAnexus, Inc. (Mountain View, CA). Results: There was no measureable evidence of uteroplacental dysfunction or fetal compromise. Conclusion: Our study is the first to show only the truncated Hltf isoform is expressed in E18.5 term placenta, and we identified a functional link between alternative splicing of Hltf and immunosuppression at the feto-maternal interface. Overall design: Placental mRNA profiles of E18.5 term placenta from five wild type control and five Hltf null mouse samples were generated by deep sequencing by Illumina HiSeq2000/2500.
Alternative splicing of helicase-like transcription factor (Hltf): Intron retention-dependent activation of immune tolerance at the feto-maternal interface.
Specimen part, Cell line, Subject
View SamplesChronic alcohol ingestion changes the alveolar landscape. We used microarrays to characterize the change in mRNA expression following chronic alcohol ingestion in male Sprague Dawley rates (EtOH 36% of calories)
Chronic ethanol exposure alters the lung proteome and leads to mitochondrial dysfunction in alveolar type 2 cells.
Sex, Specimen part
View SamplesDAP12 is a transmembrane protein, expressed as a disulfide-bonded homodimer and bears an immunoreceptor tyrosine-based activation motif (ITAM). DAP12 is broadly expressed in hematopoietic cells and associates with a variety of cell surface receptors in lymphoid and myeloid cells. Macrophages express several DAP12-associated receptors including triggering receptors expressed by myeloid cells (TREM)-1,2 and 3, myeloid DAP12-associating lectin (MDL)-1, CD200R like proteins CD200R3/R4 and CD300C/D/E .
Essential role of DAP12 signaling in macrophage programming into a fusion-competent state.
No sample metadata fields
View SamplesIn this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Global organization of replication time zones of the mouse genome.
None
Cell line, Subject
View SamplesGene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3
1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation.
No sample metadata fields
View SamplesTo identify in vivo new cardiac SRF target genes and to study the response of these novel genes to SRF overexpression, we employed a cardiac-specific, transgenic mouse model that has a phenotype in young adulthood which resembles that of the typically aged heart. Using this cardiac aging model, we identified 207 genes that are important to cardiac function that were differentially expressed in vivo. Among them, 192 genes had SRF binding motifs (56 with CArG and 136 with CArG-like elements) in their promoter region. Fifty-one of 56 genes with classic CArG elements were not previously reported. These SRF target genes were grouped into 12 categories based on their function. It was observed that genes associated with cardiac energy metabolism shifted toward that of carbohydrate metabolism and away from that of fatty acid metabolism. The expression of genes that are involved in transcription and ion regulation were decreased, but expression of cytoskeletal genes were significantly increased. Using public databases of mouse models of stress, we also found that altered expression of the SRF target genes occurred in these hearts as well. Thus, SRF target genes are actively regulated under various physiological and pathological conditions, including hemodynamic stress. The mild elevation of SRF protein in the rodent heart that is observed during typical adult aging may have a major impact on many SRF target genes, thereby affecting cardiac structure and performance. In addition, these results could help to enhance our understanding of SRF regulation of cellular processes, including metabolic and cytoskeletal function.
Identification of New SRF Binding Sites in Genes Modulated by SRF Over-Expression in Mouse Hearts.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Specimen part
View SamplesPrecise nucleosome-positioning patterns at promoters are thought to be crucial for faithful transcriptional regulation. However, the mechanisms by which these patterns are established and dynamically maintained and subsequently contribute to transcriptional control are poorly understood. The Swi/Snf (Baf) chromatin remodeling complex is a master developmental regulator and tumor suppressor that is capable of mobilizing nucleosomes in biochemical assays. Yet, its role in establishing the nucleosome landscape in vivo is unclear. Here we have inactivated Snf5 and Brg1, core subunits of the mammalian Swi/Snf complex, to evaluate their effects on chromatin structure and transcription levels genome-wide. We find that inactivation of either subunit leads to disruptions of specific nucleosome patterning combined with a loss of overall nucleosome occupancy at a large number of promoters, regardless of their association with CpG islands. These rearrangements are accompanied by gene expression changes that promote cell proliferation. Collectively, these findings define a direct relationship between chromatin-remodeling complexes, chromatin structure, and transcriptional regulation.
Swi/Snf chromatin remodeling/tumor suppressor complex establishes nucleosome occupancy at target promoters.
Specimen part
View SamplesLong noncoding RNAs (lncRNAs) are thought to be prevalent regulators of gene expression, but the consequences of lncRNA inactivation in vivo are mostly unknown. Here we show that targeted deletion of mouse Hotair lncRNA leads to de-repression of hundreds of genes, resulting in homeotic transformation of the spine and malformation of metacarpal-carpal bones. RNA-seq and conditional inactivation reveal an ongoing requirement of Hotair to repress HoxD genes and multiple imprinted loci such as Dlk1-Meg3 and Igf2-H19. Hotair binds to both Polycomb repressive complex 2 that methylates histone H3 at lysine 27 (H3K27) and Lsd1 complex that demethylates histone H3 at lysine 4 (H3K4) in vivo. Hotair inactivation causes coordinate H3K27me3 loss and H3K4me3 gain at select target genes throughout the genome. These results reveal a shared regulatory mechanism to enforce silent chromatin state at Hox and imprinted genes via Hotair lncRNA.
Targeted disruption of Hotair leads to homeotic transformation and gene derepression.
Specimen part
View SamplesTcl1 is known to be involved in survival, proliferation and differentiation of human lymphocytes and mouse embryonic stem cells. Loss of Tcl1 gene in the KO mouse model affects skin integrity inducing alopecia and ulcerations.
T Cell Leukemia/Lymphoma 1A is essential for mouse epidermal keratinocytes proliferation promoted by insulin-like growth factor 1.
Specimen part
View Samples