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.

Details

Title
Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies
Author
Boyd, Mette 1 ; Thodberg, Malte 1 ; Vitezic, Morana 1 ; Bornholdt, Jette 1 ; Vitting-Seerup, Kristoffer 1 ; Chen, Yun 1 ; Coskun, Mehmet 1 ; Li, Yuan 2 ; Bobby Zhao Sheng Lo 3 ; Klausen, Pia 4 ; Schweiger, Pawel Jan 5 ; Anders Gorm Pedersen 6   VIAFID ORCID Logo  ; Rapin, Nicolas 7   VIAFID ORCID Logo  ; Skovgaard, Kerstin 8 ; Dahlgaard, Katja 9 ; Andersson, Robin 10   VIAFID ORCID Logo  ; Thilde Bagger Terkelsen 1 ; Lilje, Berit 1 ; Troelsen, Jesper Thorvald 9 ; Andreas Munk Petersen 11 ; Kim Bak Jensen 12   VIAFID ORCID Logo  ; Ismail Gögenur 13 ; Thielsen, Peter 2 ; Jakob Benedict Seidelin 2 ; Ole Haagen Nielsen 2 ; Jacob Tveiten Bjerrum 2 ; Sandelin, Albin 1   VIAFID ORCID Logo 

1  Department of Biology, University of Copenhagen, Copenhagen N, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark 
2  Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark 
3  Department of Biology, University of Copenhagen, Copenhagen N, Denmark; Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark; Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark 
4  Department of Gastroenterology, Surgical Section, Herlev Hospital, Herlev, Denmark 
5  Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark 
6  DTU Bioinformatics, Technical University of Denmark, Lyngby, Denmark 
7  Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark; The Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen N, Denmark; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, Copenhagen N, Denmark 
8  Department of Biotechnology and Biomedicine, Technical University of Denmark, Lyngby, Denmark 
9  Department of Science and Environment (INM), Roskilde University, Roskilde, Denmark 
10  Department of Biology, University of Copenhagen, Copenhagen N, Denmark 
11  Hvidovre Hospital, Gastrounit Medical Division, University of Copenhagen, Hvidovre, Denmark; Hvidovre Hospital, Department of Clinical Microbiology, University of Copenhagen, Hvidovre, Denmark 
12  Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen N, Denmark; Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, Copenhagen N, Denmark 
13  Centre for Surgical Science, Department of Surgery, Zealand University Hospital, Koege, Denmark 
Pages
1-19
Publication year
2018
Publication date
Apr 2018
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-018-03766-z
ProQuest document ID
2030839811
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.