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

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 Pedersen, Nicolas Rapin, Kerstin Skovgaard, Katja Dahlgaard, Robin Andersson, Thilde Bagger Terkelsen, Berit Lilje, Jesper Thorvald Troelsen, Andreas Munk Petersen, Kim Bak Jensen, Ismail Gögenur, Peter Thielsen, Jakob Benedict Seidelin, Ole Haagen Nielsen, Jacob Tveiten Bjerrum () and Albin Sandelin ()
Additional contact information
Mette Boyd: University of Copenhagen
Malte Thodberg: University of Copenhagen
Morana Vitezic: University of Copenhagen
Jette Bornholdt: University of Copenhagen
Kristoffer Vitting-Seerup: University of Copenhagen
Yun Chen: University of Copenhagen
Mehmet Coskun: University of Copenhagen
Yuan Li: University of Copenhagen
Bobby Zhao Sheng Lo: University of Copenhagen
Pia Klausen: Herlev Hospital
Pawel Schweiger: University of Copenhagen
Anders Gorm Pedersen: Technical University of Denmark
Nicolas Rapin: University of Copenhagen
Kerstin Skovgaard: Technical University of Denmark
Katja Dahlgaard: Roskilde University
Robin Andersson: University of Copenhagen
Thilde Bagger Terkelsen: University of Copenhagen
Berit Lilje: University of Copenhagen
Jesper Thorvald Troelsen: Roskilde University
Andreas Munk Petersen: University of Copenhagen
Kim Bak Jensen: 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

Nature Communications, 2018, vol. 9, issue 1, 1-19

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03766-z

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DOI: 10.1038/s41467-018-03766-z

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