Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2
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Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2. / Boyd, Mette; Coskun, Mehmet; Lilje, Berit; Andersson, Robin; Hoof, Ilka; Lange, Jette Bornholdt; Dahlgaard, Katja; Olsen, Jørgen; Vitezic, Morana; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict; Nielsen, Ole Haagen; Troelsen, Jesper; Sandelin, Albin Gustav.
In: D N A Research, Vol. 21, No. 6, 2014, p. 569-583.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2
AU - Boyd, Mette
AU - Coskun, Mehmet
AU - Lilje, Berit
AU - Andersson, Robin
AU - Hoof, Ilka
AU - Lange, Jette Bornholdt
AU - Dahlgaard, Katja
AU - Olsen, Jørgen
AU - Vitezic, Morana
AU - Bjerrum, Jacob Tveiten
AU - Seidelin, Jakob Benedict
AU - Nielsen, Ole Haagen
AU - Troelsen, Jesper
AU - Sandelin, Albin Gustav
N1 - © The Author 2014. Published by Oxford University Press on behalf of Kazusa DNA Research Institute.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
U2 - 10.1093/dnares/dsu022
DO - 10.1093/dnares/dsu022
M3 - Journal article
C2 - 24990076
VL - 21
SP - 569
EP - 583
JO - DNA Research
JF - DNA Research
SN - 1340-2838
IS - 6
ER -
ID: 119409650