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Nat Commun. 2018 Apr 25;9(1):1661. doi: 10.1038/s41467-018-03766-z.

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

Author information

1
Department of Biology, University of Copenhagen, 2200, Copenhagen N, Denmark.
2
Biotech Research and Innovation Centre, University of Copenhagen, 2200, Copenhagen N, Denmark.
3
Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, 2730, Herlev, Denmark.
4
Department of Gastroenterology, Surgical Section, Herlev Hospital, 2730, Herlev, Denmark.
5
DTU Bioinformatics, Technical University of Denmark, 2800, Lyngby, Denmark.
6
The Finsen Laboratory, Rigshospitalet, University of Copenhagen, 2200, Copenhagen N, Denmark.
7
Novo Nordisk Foundation Center for Stem Cell Biology, DanStem, University of Copenhagen, 2200, Copenhagen N, Denmark.
8
Department of Biotechnology and Biomedicine, Technical University of Denmark, 2800, Lyngby, Denmark.
9
Department of Science and Environment (INM), Roskilde University, 4000, Roskilde, Denmark.
10
Hvidovre Hospital, Gastrounit Medical Division, University of Copenhagen, 2650, Hvidovre, Denmark.
11
Hvidovre Hospital, Department of Clinical Microbiology, University of Copenhagen, 2650, Hvidovre, Denmark.
12
Centre for Surgical Science, Department of Surgery, Zealand University Hospital, 4600, Koege, Denmark.
13
Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, 2730, Herlev, Denmark. jacob.wium.bjerrum@regionh.dk.
14
Department of Biology, University of Copenhagen, 2200, Copenhagen N, Denmark. albin@binf.ku.dk.
15
Biotech Research and Innovation Centre, University of Copenhagen, 2200, Copenhagen N, Denmark. albin@binf.ku.dk.

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.

PMID:
29695774
PMCID:
PMC5916929
DOI:
10.1038/s41467-018-03766-z
[Indexed for MEDLINE]
Free PMC Article

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