Identification of TNF-alpha-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    Resumé

    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.
    OriginalsprogDansk
    TidsskriftD N A Research
    Vol/bind21
    Udgave nummer6
    Sider (fra-til)569-583
    ISSN1340-2838
    DOI
    StatusUdgivet - 2014

    Citer dette

    Boyd, M., Coskun, M., Lilje, B., Andersson, R., Hoof, I., Bornholdt, J., ... Sandelin, A. (2014). Identification of TNF-alpha-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
    Boyd, Mette ; Coskun, Mehmet ; Lilje, Berit ; Andersson, Robin ; Hoof, Ilka ; Bornholdt, Jette ; Dahlgaard, Katja ; Olsen, Jørgen ; Vitezic, Morana ; Bjerrum, Jacob Tveiten Bjerrum ; Sedelin, Jakob Benedict ; Nielsen, Ole Haagen ; Troelsen, Jesper Thorvald ; Sandelin, Albin. / Identification of TNF-alpha-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2. I: D N A Research. 2014 ; Bind 21, Nr. 6. s. 569-583.
    @article{25ddab1e479247b2b52304152e20c24d,
    title = "Identification of TNF-alpha-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.",
    author = "Mette Boyd and Mehmet Coskun and Berit Lilje and Robin Andersson and Ilka Hoof and Jette Bornholdt and Katja Dahlgaard and J{\o}rgen Olsen and Morana Vitezic and Bjerrum, {Jacob Tveiten Bjerrum} and Sedelin, {Jakob Benedict} and Nielsen, {Ole Haagen} and Troelsen, {Jesper Thorvald} and Albin Sandelin",
    year = "2014",
    doi = "10.1093/dnares/dsu022",
    language = "Dansk",
    volume = "21",
    pages = "569--583",
    journal = "D N A Research",
    issn = "1340-2838",
    publisher = "Oxford University Press",
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    Boyd, M, Coskun, M, Lilje, B, Andersson, R, Hoof, I, Bornholdt, J, Dahlgaard, K, Olsen, J, Vitezic, M, Bjerrum, JTB, Sedelin, JB, Nielsen, OH, Troelsen, JT & Sandelin, A 2014, 'Identification of TNF-alpha-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2', D N A Research, bind 21, nr. 6, s. 569-583. https://doi.org/10.1093/dnares/dsu022

    Identification of TNF-alpha-Responsive Promoters and Enhancers in the Intestinal Epithelial Cell Model Caco-2. / Boyd, Mette; Coskun, Mehmet ; Lilje, Berit; Andersson, Robin; Hoof, Ilka; Bornholdt, Jette; Dahlgaard, Katja; Olsen, Jørgen; Vitezic, Morana; Bjerrum, Jacob Tveiten Bjerrum ; Sedelin, Jakob Benedict; Nielsen, Ole Haagen ; Troelsen, Jesper Thorvald; Sandelin, Albin.

    I: D N A Research, Bind 21, Nr. 6, 2014, s. 569-583.

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

    TY - JOUR

    T1 - Identification of TNF-alpha-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 - Bornholdt, Jette

    AU - Dahlgaard, Katja

    AU - Olsen, Jørgen

    AU - Vitezic, Morana

    AU - Bjerrum, Jacob Tveiten Bjerrum

    AU - Sedelin, Jakob Benedict

    AU - Nielsen, Ole Haagen

    AU - Troelsen, Jesper Thorvald

    AU - Sandelin, Albin

    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 - Tidsskriftartikel

    VL - 21

    SP - 569

    EP - 583

    JO - D N A Research

    JF - D N A Research

    SN - 1340-2838

    IS - 6

    ER -