An atlas of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54074 | GEO | 2014/07/01
SECONDARY ACCESSION(S): PRJNA234528
REPOSITORIES: GEO
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Project description:Sequencing of 5'ends of RNA molecules from Caco-2 cells +/- TNFa stimulation CAGE library construction from RNA extracted from Caco-2 cells
2014-07-01 | E-GEOD-54074 | biostudies-arrayexpress
Project description:The Caco-2 cell line is one of the most important in vitro models for enterocytes, and is used to study drug absorption and disease, including inflammatory bowel disease and cancer. In order to use the model optimally, it is necessary to map its functional entities. In this study, we have generated genome-wide maps of active transcription start sites (TSSs), and active enhancers in Caco-2 cells with or without tumour necrosis factor (TNF)-α stimulation to mimic an inflammatory state. We found 520 promoters that significantly changed their usage level upon TNF-α stimulation; of these, 52% are not annotated. A subset of these has the potential to confer change in protein function due to protein domain exclusion. Moreover, we locate 890 transcribed enhancer candidates, where ∼50% are changing in usage after TNF-α stimulation. These enhancers share motif enrichments with similarly responding gene promoters. As a case example, we characterize an enhancer regulating the laminin-5 γ2-chain (LAMC2) gene by nuclear factor (NF)-κB binding. This report is the first to present comprehensive TSS and enhancer maps over Caco-2 cells, and highlights many novel inflammation-specific promoters and enhancers.
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Project description:The series was designed to obtain gene expression patterns of TNF-alpha stimulated CaCo-2 cells. Keywords: TNF-alpha stimulation This series represents a group of 18 samples in 2 groups: 10 samples derived from not stimulated CaCo-2 cells, 8 samples from CaCo-2 cells stimulated with TNF-alpha in final concentration of 5 ng/ml for 60 min.
2010-06-25 | E-GEOD-10108 | biostudies-arrayexpress
Project description:The series was designed to obtain gene expression patterns of TNF-alpha stimulated CaCo-2 cells. Keywords: TNF-alpha stimulation
2008-02-29 | GSE10108 | GEO
Project description:In Metazoans, transcription of most genes is driven by the use of multiple alternative promoters. Although the precise regulation of alternative promoters is important for proper gene expression, the mechanisms that mediates their differential utilization remains unclear. Here, we investigate how the two alternative promoters (P1, P2) that drive MYC expression are regulated. We find that P1 and P2 can be differentially regulated across cell-types and that their selective usage is largely mediated by distal regulatory sequences. Moreover, we show that in colon carcinoma cells, Wnt-responsive enhancers preferentially upregulate transcription from the P1 promoter using reporter assays and in the context of the endogenous Wnt induction. In addition, multiple enhancer deletions using CRISPR/Cas9 corroborate the regulatory specificity of P1. Finally, we show that preferential activation between Wnt-responsive enhancers and the P1 promoter is influenced by the distinct core promoter elements that are present in the MYC promoters. Taken together, our results provide new insight into how enhancers can specifically target alternative promoters and suggest that formation of these selective interactions could allow more precise combinatorial regulation of transcription initiation.
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Project description:14 day old Caco-2 and T84 cells were treated with flagellin, lymphotox beta or TNF alpha, respectively, and their expression profile compared to non-stimulated cells. Keywords: other
2004-06-16 | GSE1474 | GEO
Project description:Silver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that the majority of surfactant coated silver nanoparticles are not taken up into differentiated Caco-2 cells. and probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFĸB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.
2015-11-13 | GSE62253 | GEO
Project description:Effect of Lactobacillus plantarum MB452 on the gene expression of the intestinal epithelial cell line Caco-2 using a reference design Experiment Overall Design: Effect of Lactobacillus plantarum MB452 on the gene expression of the intestinal epithelial cell line Caco-2 using a reference design
2009-10-09 | E-GEOD-18372 | biostudies-arrayexpress
Project description:Cells in renewing tissues exhibit dramatic transcriptional changes as they differentiate. The contribution of chromatin looping to tissue renewal is incompletely understood. Enhancer-promoter interactions could be relatively stable as cells transition from progenitor to differentiated states; alternatively, chromatin looping could be as dynamic as the gene expression from their loci. The intestinal epithelium is the most rapidly renewing mammalian tissue. Proliferative cells in crypts of Lieberkühn sustain a stream of differentiated cells that are continually shed into the lumen. We apply chromosome conformation capture combined with chromatin immunoprecipitation (HiChIP) and sequencing to measure enhancer-promoter interactions in progenitor and differentiated cells of the intestinal epithelium. Despite dynamic gene regulation across the differentiation axis, we find that enhancer-promoter interactions are relatively stable. Functionally, we find HNF4 transcription factors are required for chromatin looping at target genes. Depletion of HNF4 disrupts local chromatin looping, histone modifications, and target gene expression. This study provides insights into transcriptional regulatory mechanisms governing homeostasis in renewing tissues.
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Project description:Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of food compounds on (intestinal) health. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were incubated with in vitro digested onion extracts for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify onion-induced gene expression profiles in Caco-2 cells, digested yellow onion and white onion samples were compared to a digest control samples. Results: We found that yellow onion (n=5586, p<0.05) had a more pronounced effect on gene expression than white onion (n=3688, p<0.05). However, a substantial number of genes (n=3281, p<0.05) were affected by both onion variants in the same direction. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Conclusion: our data indicate that the in vitro Caco-2 intestinal model can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.
2016-09-16 | GSE83893 | GEO