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Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies

Author

Listed:
  • Mette Boyd

    (University of Copenhagen
    University of Copenhagen)

  • Malte Thodberg

    (University of Copenhagen
    University of Copenhagen)

  • Morana Vitezic

    (University of Copenhagen
    University of Copenhagen)

  • Jette Bornholdt

    (University of Copenhagen
    University of Copenhagen)

  • Kristoffer Vitting-Seerup

    (University of Copenhagen
    University of Copenhagen)

  • Yun Chen

    (University of Copenhagen
    University of Copenhagen)

  • Mehmet Coskun

    (University of Copenhagen
    University of Copenhagen)

  • Yuan Li

    (University of Copenhagen)

  • Bobby Zhao Sheng Lo

    (University of Copenhagen
    University of Copenhagen
    University of Copenhagen)

  • Pia Klausen

    (Herlev Hospital)

  • Pawel Schweiger

    (University of Copenhagen)

  • Anders Gorm Pedersen

    (Technical University of Denmark)

  • Nicolas Rapin

    (University of Copenhagen
    University of Copenhagen
    University of Copenhagen)

  • Kerstin Skovgaard

    (Technical University of Denmark)

  • Katja Dahlgaard

    (Roskilde University)

  • Robin Andersson

    (University of Copenhagen)

  • Thilde Bagger Terkelsen

    (University of Copenhagen
    University of Copenhagen)

  • Berit Lilje

    (University of Copenhagen
    University of Copenhagen)

  • Jesper Thorvald Troelsen

    (Roskilde University)

  • Andreas Munk Petersen

    (University of Copenhagen
    University of Copenhagen)

  • Kim Bak Jensen

    (University of Copenhagen
    University of Copenhagen)

  • Ismail Gögenur

    (Zealand University Hospital)

  • Peter Thielsen

    (University of Copenhagen)

  • Jakob Benedict Seidelin

    (University of Copenhagen)

  • Ole Haagen Nielsen

    (University of Copenhagen)

  • Jacob Tveiten Bjerrum

    (University of Copenhagen)

  • Albin Sandelin

    (University of Copenhagen
    University of Copenhagen)

Abstract

Inflammatory bowel disease (IBD) is a chronic intestinal disorder, with two main types: Crohn’s disease (CD) and ulcerative colitis (UC), whose molecular pathology is not well understood. The majority of IBD-associated SNPs are located in non-coding regions and are hard to characterize since regulatory regions in IBD are not known. Here we profile transcription start sites (TSSs) and enhancers in the descending colon of 94 IBD patients and controls. IBD-upregulated promoters and enhancers are highly enriched for IBD-associated SNPs and are bound by the same transcription factors. IBD-specific TSSs are associated to genes with roles in both inflammatory cascades and gut epithelia while TSSs distinguishing UC and CD are associated to gut epithelia functions. We find that as few as 35 TSSs can distinguish active CD, UC, and controls with 85% accuracy in an independent cohort. Our data constitute a foundation for understanding the molecular pathology, gene regulation, and genetics of IBD.

Suggested Citation

  • Mette Boyd & Malte Thodberg & Morana Vitezic & Jette Bornholdt & Kristoffer Vitting-Seerup & Yun Chen & Mehmet Coskun & Yuan Li & Bobby Zhao Sheng Lo & Pia Klausen & Pawel Schweiger & Anders Gorm Pede, 2018. "Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies," Nature Communications, Nature, vol. 9(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03766-z
    DOI: 10.1038/s41467-018-03766-z
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