This SuperSeries is composed of the SubSeries listed below.
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Specimen part
View SamplesThe oral cavity is the persistent reservoir for EBV with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns that are regulated by epigenetic modifications involving DNA methylation and chromatin structure. Such regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may inadvertently result in long-lasting, oncogenic host epigenetic reprogramming. To test this hypothesis in the context of EBV infection of epithelial cells, we established a transient infection model to identify the epigenetic consequences after EBV infection of immortalized normal oral keratinocytes and subsequent viral loss.
Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.
Specimen part
View SamplesMyocarditis is an inflammatory disease in the heart and is mainly caused by viral infections. Viral myocarditis has been proposed to be divided into three phases; the acute viral phase, the subacute immune phase, and the chronic cardiac remodeling phase. Although individualized therapy should be applied depending on the phase, no clinical or experimental studies have found biomarkers that distinguish between the three phases of myocarditis. Theilers murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, and can cause myocarditis in susceptible mouse strains. Using this novel model for viral myocarditis induced with TMEV, we conducted multivariate analysis including echocardiography, serum troponin and viral RNA titration, and microarray for identifying the biomarker candidates that discriminate the three phases. Using C3H mice infected with TMEV on 4, 7, and 60 days post infection (p.i.), we conducted bioinformatics analyses, including principal component analysis (PCA) of microarray data, since our traditional cardiac and serum assays, including two-way comparison of microarray data, did not lead to the identification of a single biomarker. PCA separated heart samples clearly between the groups of 4, 7, and 60 days p.i. Representative genes contributing to the separation were as follows: 4 and 7 days p.i., innate immunity-related genes, such as Irf7, and Cxcl9; 7 and 60 days p.i., acquired immunity-related genes, such as Cd3g and H2-Aa; and cardiac remodeling-related genes, such as Mmp12 and Gpnmb. Here, sets of molecules, but not a single molecule, identified by the unsupervised PCA, were found to be useful as the phase-specific biomarkers.
Bioinformatics multivariate analysis determined a set of phase-specific biomarker candidates in a novel mouse model for viral myocarditis.
Sex, Specimen part, Time
View SamplesWe have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive UCC, respectively
Identification of genes correlated with early-stage bladder cancer progression.
Specimen part
View SamplesPatients with systemic lupus erythematosus (SLE) have a markedly increased risk to develop cardiovascular disease, and traditional cardiovascular risk factors fail to account for this increased risk. We used microarray to probe the platelet transcriptome in individuals with SLE and healthy controls, and the gene and protein expression of a subset of differentially expressed genes was further investigated and correlated to platelet activation status. Real-time PCR was used to confirm a type I interferon (IFN) gene signature in patients with SLE, and the IFN-regulated proteins PRKRA, IFITM1 and CD69 (p<0.0001) were found to be up-regulated in platelets from SLE patients as compared to healthy volunteers. Notably, patients with a history of vascular disease had increased expression of type I IFN-regulated proteins as well as more activated platelets as compared with patients without vascular disease. We suggest that interferogenic immune complexes stimulate production of IFN which up-regulates the megakaryocytic type I IFN-regulated genes and proteins. This could affect platelet activation and contribute to development of vascular disease in SLE. In addition, platelets with type I IFN signature could be a novel marker for vascular disease in SLE.
Platelet transcriptional profile and protein expression in patients with systemic lupus erythematosus: up-regulation of the type I interferon system is strongly associated with vascular disease.
Sex, Age, Specimen part, Disease
View SamplesWe interrogated the transcriptome using RNA-seq at several stages of an mouse embryonic stem cell to cardiomyocyte directed differentiation protocol. These four stages represent timepoints when differentiating cultures are enriched for embryonic stem cells (ESC), mesodermal cells (MES), cardiac precursors (CP), or cardiomyocytes (CM) respectively. This study revealed many dynamic patterns of mRNAs and long non-coding RNAs (lncRNAs) and identified groups of genes with similar expression patterns during differentiation. Overall design: RNA-seq analysis of global RNA levels at 4 stages of directed cardiac differentiation of mouse embryonic stem cells. Each stage in biological duplicates
Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage.
Specimen part, Cell line, Subject, Time
View SamplesThe importance of the role of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore co-expressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of mir-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in highly penetrant pleiotropic developmental defects. We further show that this novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and likely reflects the more general cis-regulation of expression of individual miRNAs. Thus, our results reveal a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift biological response. Overall design: RNA was extracted from Drosophila third instar larval eye discs of animals grown in standard conditions; Illumina HiSeq2000 Next Gen RNA Sequencing was performed, and differential expression of genes was assessed in wild-type vs unchecked miR-998 expression
Novel regulation and functional interaction of polycistronic miRNAs.
Specimen part, Subject
View SamplesExpression of dE2F1 induces proliferation and apoptosis. We sought to perform an unbiased analysis of the effect of co-expression of miR-11
mir-11 limits the proapoptotic function of its host gene, dE2f1.
Specimen part
View SamplesThe GntR-like protein NorG has been shown to affect Staphylococcus aureus genes involved in the resistance to quinolones and beta-lactams such as those encoding the NorB and AbcA transporters. To identify the target genes regulated by NorG, we carried out transcriptional profiling assays using S. aureus RN6390 and its isogenic norG::cat mutant. Our data showed that NorG positively affected the transcription of global regulators mgrA, arlS, and sarZ. The three putative drug efflux pump genes most positively affected by NorG were the NorB efflux pump (5.1-fold), the MmpL-like protein SACOL2566 (5.2-fold), and the BcrA-like drug transporter SACOL2525 (5.7-fold). The S. aureus predicted MmpL protein showed 53% homology with the MmpL lipid transporter of Mycobacterium tuberculosis, and the putative SACOL2525 protein showed 87% homology with the bacitracin drug transporter BcrA of Staphylococcus hominis. Two pump genes most negatively affected by NorG were NorC (4-fold) and AbcA (6-fold). Other categories of genes such as those participating in amino acid, inorganic ion, or nucleotide transporters and metabolism, were also affected by NorG. Real-time RT-PCR assays for mgrA, arlS, sarZ, norB, norC, abcA, mmpL, and bcrA-like were carried out to verify microarray data and showed the same level of up- or down regulation by NorG. The norG mutant showed a twofold increase in the resistance to norfloxacin and rhodamine, both substrates of the NorC transporter, which is consistent with the resistance phenotype conferred by overexpression of norC on a plasmid. These data indicate that NorG has broad regulatory function in S. aureus.
Transcriptional profiling analysis of the global regulator NorG, a GntR-like protein of Staphylococcus aureus.
No sample metadata fields
View SamplesWe implemented a functional genomics approach as a means to undertake a large-scale analysis of the Xenopus laevis inner ear transcriptome through microarray analysis.
Probing the Xenopus laevis inner ear transcriptome for biological function.
Specimen part
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