1. Identification of TNF- -Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2
- Author
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Jakob Benedict Seidelin, Katja Dahlgaard, Mette Boyd, Ole Haagen Nielsen, Robin Andersson, Albin Sandelin, Jørgen Olsen, Jesper T. Troelsen, Berit Lilje, Ilka Hoof, Morana Vitezic, Mehmet Coşkun, Jette Bornholdt, and Jacob Tveiten Bjerrum
- Subjects
transcribed enhancers ,Enhancer RNAs ,Biology ,Response Elements ,Genetics ,Transcriptional regulation ,Humans ,transcriptional regulation ,alternative promoters ,Enhancer ,Molecular Biology ,Gene ,Transcription Initiation, Genetic ,Tumor Necrosis Factor-alpha ,NF-kappa B ,Chromosome Mapping ,Promoter ,General Medicine ,Full Papers ,NFKB1 ,Cell biology ,inflammation ,Cell culture ,non-coding RNAs ,Tumor necrosis factor alpha ,Laminin ,Caco-2 Cells ,Genome-Wide Association Study - Abstract
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.
- Published
- 2014