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DNA Res. 2014 Dec;21(6):569-83. doi: 10.1093/dnares/dsu022. Epub 2014 Jul 2.

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

Author information

1
The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaloes Vej 5, Copenhagen DK-2200, Denmark.
2
The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaloes Vej 5, Copenhagen DK-2200, Denmark Department of Gastroenterology, Medical Section, University of Copenhagen, Herlev Hospital, Herlev DK-2730, Denmark.
3
Department of Science, Systems and Models, Roskilde University, Roskilde DK-4000, Denmark.
4
Department of Cellular and Molecular Medicine, The Panum Institute, University of Copenhagen, Copenhagen N DK-2200, Denmark.
5
Department of Gastroenterology, Medical Section, University of Copenhagen, Herlev Hospital, Herlev DK-2730, Denmark.
6
The Bioinformatics Centre, Department of Biology & Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaloes Vej 5, Copenhagen DK-2200, Denmark albin@binf.ku.dk.

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.

KEYWORDS:

alternative promoters; inflammation; non-coding RNAs; transcribed enhancers; transcriptional regulation

PMID:
24990076
PMCID:
PMC4263293
DOI:
10.1093/dnares/dsu022
[Indexed for MEDLINE]
Free PMC Article

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