Dysregulation of ceramide synthesis has been associated with metabolic disorders such as atherosclerosis and diabetes mellitus. Using a human hepatoma cell line (Huh7), we investigated the changes in lipid homeostasis and gene expression when the synthesis of ceramide is perturbed by knocking down serine transferases subunits 1, 2 and 3 (SPTLC123) or dihydroceramide desaturase (DEGS1). While the inhibition of serine palmitoyl transferase (SPTLC) affects ceramide production differently at the subspecies level depending upon which SPTLC subunit is silenced; depleting DEGS1 is sufficient to produce a similar outcome as knocking down all SPTLC subunits. Both the distribution of multiple lipid classes, especially at the subspecies level, and the global transcriptional profile is altered differently when either SPTLC123 or DEGS1 were silenced. The overall transcriptional changes indicate a negative regulation in biosynthetic processes and a down-regulation of genes involved in general endomembrane trafficking for both DEGS1 and SPTLC123 siRNA treated cells, but also the up-regulation of genes involved with cell migration function in DEGS1 siRNA cells. Pathway analysis indicate changes in amino acid, sugar and nucleotide metabolisms as well as vesicle trafficking between organelles occurred more robustly in DEGS1 silenced cells. Although either SPTLC123 or DEGS1 siRNA treatment positively regulated numerous genes involved with endocytosis and endosomal recycling, depleting SPTLC123 caused transcriptional changes in genes primarily involved with lipid metabolism. The alterations reflect how SPTLC or DEGS1 silenced cells respond differently to disruption in lipid flux, but also maintain cellular lipid pools through increasing endocytotic processes and down-regulating metabolic biosynthesis without developing endoplasmic reticulum stress. Also, these results are the first to demonstrate that reducing ceramide synthesis by decreasing the function of either SPTLC or DEGS1 affects cellular function differently at the level of lipid synthesis and gene expression.
Silencing of enzymes involved in ceramide biosynthesis causes distinct global alterations of lipid homeostasis and gene expression.
Cell line
View SamplesLysine 9 di-methylation and lysine 27 tri-methylation of histone H3 (H3K9me2 and H3K27me3) are mostly linked to gene repression. However, functions of repressive histone methylation dynamics during inflammatory responses remain poorly understood. Here, we show that lysine demethylase 7A (KDM7A) and 6A (UTX) are rapidly transported to nuclear factor kappa-B (NF-?B) related elements in human endothelial cells in response to tumor necrosis factor (TNF)-a. KDM7A and UTX demethylate H3K9me2 and H3K27me3, respectively, and cooperatively activate NF-?B dependent inflammatory genes. Furthermore, using both in situ Hi-C and other 3C based technology, loops between super enhancers (SEs) are newly formed following TNF-a-stimuli at NF-?B-dependent inflammatory loci where KDM7A- and UTX-recruitment coincide. Collectively, these findings suggest that erasing of repressive histone marks by KDM7A and UTX within NF-?B-related elements might functionally associate with formation of SE-SE three-dimensional interactions and could be a cue signal during inflammatory responses in human endothelial cells. Overall design: Total 29 samples were derived from [1] HUVECs in the absence or presence of TNF-alpha (0, 4, and 24 hrs) to determine TNF-alpha-responsive genes during inflammation, [2] si control, siKDM7A, siUTX, or siKDM7A+siUTX transfected HUVECs under TNF-alpha-stimuli (4 hrs) to understand molecular function of KDM7A and UTX during inflammation.
Coordinated demethylation of H3K9 and H3K27 is required for rapid inflammatory responses of endothelial cells.
Subject, Time
View SamplesRecently the role of PPAR/ in angiogenesis has been revealed, and we hypothesized that the crosstalk between hypoxia and PPAR/ on endothelial cells may exsist. To elucidate the interaction between two signalings, we report the comprehensive change of transcripts induced by PPAR/ agonist (GW501516) and/or hypoxia.
Cross-enhancement of ANGPTL4 transcription by HIF1 alpha and PPAR beta/delta is the result of the conformational proximity of two response elements.
Specimen part
View SamplesRNA-sequencing for 6 samples Overall design: Examing 2 conditions, each with 3 replicates
Integrated analysis of long non-coding RNAs and mRNAs associated with peritendinous fibrosis.
Specimen part, Subject
View SamplesScalp psoriasis shows a variable clinical spectrum and in many cases poses a great therapeutic challenge. However, it remains unknown whether the immune response of scalp psoriasis differs from understood pathomechanisms of psoriasis on other skin areas. We sought to determine the cellular and mollecular phenotype of scalp psoriasis by performing a comparative analysis of scalp vs skin using lesional and nonlesional samples from 20 Caucasian subjects with untreated moderate to severe psoriasis and significant scalp involvement, and 10 control subjects without psoriasis. Our results suggest that even in the scalp psoriasis is a disease of the inter-follicular skin. The immune mechanisms that mediate scalp psoriasis were found to be similar to those involved in skin psoriasis. However, the magnitude of dysregulation, number of differentially expressed genes, and enrichment of the psoriatic genomic fingerprinting were more prominent in skin lesions. Furthermore, the scalp transcriptome showed increased modulation of several gene-sets, particularly those induced by interferon-gamma, compared with skin psoriasis which was mainly associated with activation of TNF/L-17/IL-22-induced keratinocyte response genes. We also detected differences in expression of gene-sets involving negative regulation, epigenetic regulation, epidermal differentiation, and dendritic cell or Th1/Th17/Th22-related T-cell processes.
Molecular and Cellular Profiling of Scalp Psoriasis Reveals Differences and Similarities Compared to Skin Psoriasis.
Specimen part, Disease, Disease stage
View SamplesThe focus of this study was to identify changes in host gene expression induced by the transcription-dependent function of the viral AC2 protein, and induced by the interaction of AC2/C2 with SnRK1.2 (AtAKIN11).
Altered expression of Arabidopsis genes in response to a multifunctional geminivirus pathogenicity protein.
Age, Specimen part, Treatment
View SamplesThe ubiquitously expressed RNA-binding protein Hu Antigen R (HuR) or ELAVL1 is implicated in a variety of biological processes as well as being linked with a number of diseases, including cancer. Despite a great deal of prior investigation into HuR, there is still much to learn about its function. We take an important step in this direction by conducting iCLIP (CrossLinking and ImmunoPreciptation) and RNA Sequencing experiments followed by an extensive computational analysis to determine the characteristics of the HuR binding site and impact on the transcriptome. We reveal that HuR targets predominantly uracil-rich single-stranded stretches of varying size, with a strong conservation of structure and sequence composition. Despite the fact that HuR sites are observed in intronic regions, our data does not support a role for HuR in regulating splicing. HuR sites in 3'UTRs overlap extensively with predicted miRNA target sites suggesting interplay between the functions of HuR and miRNAs. Network analysis showed that identified targets containing HuR binding sites in the 3' UTR are highly interconnected.
Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex network of target genes and novel characteristics of its binding sites.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesTo determine differential gene expression in peripheral blood of asthmatic individuals undergoing allergen inhalation challenge, post-challenge compared to pre-challenge
Peripheral blood gene expression changes during allergen inhalation challenge in atopic asthmatic individuals.
Sex, Age, Specimen part
View SamplesAbiotic stress is a major environmental factor that limits cotton growth and yield, moreover, this problem has become more and more serious recently and multiple stresses often occur simultaneously due to the global climate change and environmental pollution.
Transcriptome analysis reveals crosstalk of responsive genes to multiple abiotic stresses in cotton (Gossypium hirsutum L.).
Specimen part
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