We identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes.
A quantitative model of transcriptional regulation reveals the influence of binding location on expression.
Specimen part
View SamplesMyocardial infarction (MI) often results in left ventricular (LV) remodeling followed by heart failure (HF). It is of great clinical importance to understand the molecular mechanisms that trigger transition from compensated LV injury to HF and to identify relevant diagnostic biomarkers. In this study, we performed transcriptional profiling of LVs in rats with a wide range of experimentally induced infarct sizes and of peripheral blood mononuclear cells (PBMCs) in animals that developed HF.
Transcriptional profiling of left ventricle and peripheral blood mononuclear cells in a rat model of postinfarction heart failure.
Specimen part
View SamplesWe report the application of RNA sequencing technology for high-throughput profiling of gene expression responses to human rhinovirus infection at 24 hours in air-liquid interface human airway epithelial cell cultures derived from 6 asthmatic and 6 non-asthmatic donors. RNA-seq analysis identified sets of genes associated with asthma specific viral responses. These genes are related to inflammatory pathways, epithelial remodeling and cilium assembly and function, including those described previously (e.g. CCL5, CXCL10 and CX3CL1), and novel ones that were identified for the first time in this study (e.g. CCRL1, CDHR3). We concluded that air liquid interface cultured human airway epithelial cells challenged with live HRV are a useful in vitro model for the study of rhinovirus induced asthma exacerbation, given that our findings are consistent with clinical data sets. Furthermore, our data suggest that abnormal airway epithelial structure and inflammatory signaling are important contributors to viral induced asthma exacerbation. Overall design: Differentiated air-liquid interface cultured human airway epithelial cell mRNA profiles from 6 asthmatic and 6 non-asthmatic donors after 24 hour treatment with either HRV or vehicle control were generated by deep sequencing, using Illumina HiSeq 2000.
Phenotypic responses of differentiated asthmatic human airway epithelial cultures to rhinovirus.
No sample metadata fields
View SamplesMechanical forces are essential for normal fetal lung development. However, the cellular and molecular mechanisms regulating this process remain largely unknown. In the present study, we used oligonucleotide microarray technology to investigate gene expression profile in cultured E19 rat fetal lung type II epithelial cells exposed to a level of mechanical strain similar to that observed in utero. Significance Analysis of Microarrays (SAM) identified 92 genes differentially expressed by strain. Interestingly, several members of the solute carrier family of amino acid transporters, genes involved in amino acid synthesis and development, and amiloride-sensitive epithelial sodium channel gene were induced by strain. These results were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Thus, this study identifies genes induced by strain that may be important for amino acid signaling pathways, protein synthesis and development in fetal type II cells. In addition, these data suggest that mechanical forces may contribute to facilitate lung fluid reabsorption in preparation for birth. Taken together, the present investigation provides further insights into how mechanical forces may modulate fetal lung development.
DNA microarray reveals novel genes induced by mechanical forces in fetal lung type II epithelial cells.
Sex, Specimen part
View SamplesDNA methylation is an epigenetic mark thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells with a live pathogenic bacteria is associated with rapid changes in methylation levels at thousands of loci. We performed an integrated analysis of data on genome-wide DNA methylation, histone mark patterns, chromatin accessibility, and gene expression, before and after infection. We found that infection-induced changes in methylation rarely occur at promoter regions and instead localize to distal enhancer elements. Active demethylation is associated with extensive epigenetic remodeling, including the gain of histone activation marks and the induction of enhancer RNAs, and is strongly predictive of changes in the expression levels of nearby genes. Collectively, our observations show that active, rapid changes in DNA methylation in enhancers play a previously unappreciated role in regulating the transcriptional response of immune cells to infection. Overall design: Transcriptional profiles (polyA+) of 6 non-infected and 6 MTB-infected dendritic cell samples.
Bacterial infection remodels the DNA methylation landscape of human dendritic cells.
No sample metadata fields
View SamplesHeart failure (HF) is the most common cause of morbidity and mortality in the developed countries, especially considering the present demographic tendencies in those populations.
Gene expression profiling reveals potential prognostic biomarkers associated with the progression of heart failure.
Specimen part
View SamplesDespite a substantial progress in diagnosis and therapy, acute myocardial infarction (MI) is a major cause of mortality in the general population. A novel insight into the pathophysiology of myocardial infarction obtained by studying gene expression should help to discover novel biomarkers of MI and to suggest novel strategies of therapy. The aim of our study was to establish gene expression patterns in leukocytes from acute myocardial infarction patients.
Altered gene expression pattern in peripheral blood mononuclear cells in patients with acute myocardial infarction.
Specimen part, Subject
View SamplesSoybean aphids are phloem-feeding pests that can cause significant yield losses in soybean plants. Soybean aphids thrive on susceptible soybean lines but not on resistant lines.
Multiple phytohormone signals control the transcriptional response to soybean aphid infestation in susceptible and resistant soybean plants.
Specimen part
View SamplesChromosome 5q deletions (del(5q)) are common in high-risk (HR) Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR-MDS/AML and miR-146a-/- hematopoietic stem/progenitor cells (HSPC) results in TRAF6/NF- activation. Increased survival and proliferation of HSPC from miR-146alow HR-MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-B-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-B signaling, as disrupting the p62-TRAF6 signaling complex results in cell cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR-MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-B to sustain TRAF6/NF-B signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network.
Sex, Specimen part
View SamplesFollow-up work was performed for SF3A2, a gene among the hits identified in a red blood cell trait GWAS-informed shRNA screen. Differential splicing effects were assayed to investigate resulting effects on the differentiating erythroid cell spliceome and explore potential modifier relationships with other known splicing defects associated with human disease. Overall design: Examination of differential splicing events resulting from knockdown of splicing factor 3a subunit 2 (SF3A2) in three unique donor CD34+ cells populations undergoing erythroid differentiation. Two shRNA targeting SF3A2 were tested, along with a negative control shRNA targeting luciferase (which should not be expressed) using paired-end sequencing.
Gene-centric functional dissection of human genetic variation uncovers regulators of hematopoiesis.
Specimen part, Subject
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