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

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

doi:10.1093/dnares/dsu022

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

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

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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.

Original language	English
Journal	D N A Research
Volume	21
Issue number	6
Pages (from-to)	569-583
Number of pages	15
ISSN	1340-2838
DOIs	https://doi.org/10.1093/dnares/dsu022
Publication status	Published - 1 Dec 2014

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Identification of TNF-α-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2Final published version, 1 MB

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Boyd, M., Coskun, M., Lilje, B., Andersson, R., Hoof, I., Lange, J. B., Dahlgaard, K., Olsen, J., Vitezic, M., Bjerrum, J. T., Seidelin, J. B., Nielsen, O. H., Troelsen, J., & Sandelin, A. G. (2014). Identification of TNF-α-responsive promoters and enhancers in the intestinal epithelial cell model Caco-2. D N A Research, 21(6), 569-583. https://doi.org/10.1093/dnares/dsu022

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

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.",

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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

PY - 2014/12/1

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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

SN - 1340-2838

VL - 21

SP - 569

EP - 583

JO - D N A Research

JF - D N A Research

IS - 6

ER -

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

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