DNA 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 SamplesGiven the heterogeneity of disease evident from study of the presentation, histomorphology, disease course, and molecular lesions of bladder cancer, a cohort of 8 non-muscle invasive and 11 muscle invasive bladder cancers were profiled for gene expression using the Affymetrix HG-U133A platform.
Transcriptional signatures of Ral GTPase are associated with aggressive clinicopathologic characteristics in human cancer.
No sample metadata fields
View SamplesWe used Arabidopsis full-genome microarrays to characterize plant transcript accumulations at different stages of infection with the biotrophic oomycete downy mildew pathogen, Hyaloperonospora arabidopsidis : initiation (< 1 dpi) and maintenance of infection (> 4 dpi).
An Arabidopsis (malectin-like) leucine-rich repeat receptor-like kinase contributes to downy mildew disease.
Specimen part
View SamplesB16F1 cells are a good model to study cell motility and cytoskeletal organization. In our lab, a combination of microscopy and gene silencing was used to approach the problem. Having gene expression profiles for B16F1 would facilitate and support subsequent gene silencing by RNAi as well as potentially identify new molecular players.
Role of fascin in filopodial protrusion.
No sample metadata fields
View SamplesGene fusions arising from chromosomal translocations are key oncogenic drivers in soft tissue sarcomas but little is known about how they exert their oncogenic effects. Our study explores the molecular mechanisms by which the SS18-SSX fusion oncoprotein subverts epigenetic mechanisms of gene regulation to drive synovial sarcoma. Using functional genomics, we identify KDM2B – a histone demethylase and core component of a non-canonical Polycomb Repressive Complex 1 (PRC1.1) – as selectively required for sustaining synovial sarcoma cell transformation. SS18-SSX physically interacts with PRC1.1 and co-associates with SWI/SNF and KDM2B complexes on unmethylated CpG islands genome-wide. Via KDM2B, SS18-SSX binds and aberrantly activates expression of a series of developmentally regulated transcription factors that would otherwise be targets of polycomb-mediated repression, which is restored upon KDM2B depletion leading to irreversible mesenchymal differentiation. Thus, SS18-SSX de-regulates developmental programs to drive transformation by hijacking a transcriptional repressive complex to aberrantly activate gene expression. Overall design: RNA-Seq of human synovial sarcoma cells (HS-SY-II) in control cells (Ren.173) and upon knockdown of SS18-SSX1 (SS18.273 and SSX.1274) or of KDM2B (KDM2B. 4395 and KDM2B.4835) in duplicates.
The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma.
Subject
View SamplesClinical heterogeneity of esrtrogen receptor-negative, progesterone receptor-negative [ER(-)/PR(-)] breast cancer (BC) suggests biological heterogeneity. We performed gene expression analysis of primary BCs and BC cell lines to identify the underlying biology of ER(-)/PR(-) disease, define subsets, and identify potential therapeutic targets.
An estrogen receptor-negative breast cancer subset characterized by a hormonally regulated transcriptional program and response to androgen.
Specimen part, Disease, Disease stage, Treatment
View SamplesThe mucosa that lines the respiratory and gastrointestinal (GI) tracts is an important portal of entry for pathogens and provides the frontline of immune defense against HIV infection. Using the simian immunodeficiency virus (SIV) rhesus macaque model, we have performed a comparative analysis of host gene expression in the lung and GI mucosa in response to SIV infection and antiretroviral therapy.
Enhanced innate antiviral gene expression, IFN-α, and cytolytic responses are predictive of mucosal immune recovery during simian immunodeficiency virus infection.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
Specimen part, Disease, Disease stage, Cell line, Treatment
View SamplesA majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease.
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
Specimen part, Disease, Disease stage
View SamplesA majority of individuals infected with human immunodeficiency virus (HIV) have inadequate access to antiretroviral therapy and ultimately develop debilitating oral infections that often correlate with disease progression. Our study evaluates the potential of simian immunodeficiency virus (SIV) infected rhesus macaques to serve as a non-human primate model for oral manifestations of HIV disease.
Transcription profiling reveals potential mechanisms of dysbiosis in the oral microbiome of rhesus macaques with chronic untreated SIV infection.
Specimen part, Disease, Disease stage
View Samples