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Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2

Publikation: Bidrag til tidsskriftTidsskriftartikel

Mette Boyd, Mehmet Coskun, Berit Lilje, Robin Andersson, Ilka Hoof, Jette Bornholdt Lange, Katja Dahlgaard, Jørgen Olsen, Morana Vitezic, Jacob Tveiten Bjerrum, Jakob Benedict Seidelin, Ole Haagen Nielsen, Jesper Troelsen, Albin Gustav Sandelin

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.

OriginalsprogEngelsk
TidsskriftD N A Research
Vol/bind21
Tidsskriftsnummer6
Sider (fra-til)569-583
Antal sider15
ISSN1340-2838
DOI
StatusUdgivet - 2014

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