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

Boyd, Mette ; Vitezic, Morana ; Bornholdt, Jette ; Vitting-Seerup, Kristoffer ; Chen, Yun ; Coskun, Mehmet ; Li, Yuan ; Lo, Bobby Zhao Sheng ; Klausen, Pia and Jan Schweiger, Pawel , et al. (2018) In Nature Communications 9(1).
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... (More)

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.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Adult, Biopsy, Case-Control Studies, Cohort Studies, Colitis, Ulcerative/diagnosis, Colon/diagnostic imaging, Colonoscopy, Crohn Disease/diagnosis, Female, Humans, Intestinal Mucosa/diagnostic imaging, Male, Middle Aged, Polymorphism, Single Nucleotide, Regulatory Sequences, Nucleic Acid/genetics, Sequence Analysis, RNA, Up-Regulation
in
Nature Communications
volume
9
issue
1
article number
1661
pages
19 pages
publisher
Nature Publishing Group
external identifiers
  • pmid:29695774
  • scopus:85046090244
ISSN
2041-1723
DOI
10.1038/s41467-018-03766-z
language
English
LU publication?
no
id
34434060-7775-4fa0-9c1f-4771fdce9372
date added to LUP
2019-04-10 13:14:13
date last changed
2021-04-13 01:03:32
@article{34434060-7775-4fa0-9c1f-4771fdce9372,
  abstract     = {<p>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.</p>},
  author       = {Boyd, Mette and Vitezic, Morana and Bornholdt, Jette and Vitting-Seerup, Kristoffer and Chen, Yun and Coskun, Mehmet and Li, Yuan and Lo, Bobby Zhao Sheng and Klausen, Pia and Jan Schweiger, Pawel and Pedersen, Anders Gorm and Rapin, Nicolas and Skovgaard, Kerstin and Dahlgaard, Katja and Andersson, Robin and Terkelsen, Thilde Bagger and Lilje, Berit and Troelsen, Jesper Thorvald and Petersen, Andreas Munk and Jensen, Kim Bak and Gögenur, Ismail and Thielsen, Peter and Seidelin, Jakob Benedict and Nielsen, Ole Haagen and Bjerrum, Jacob Tveiten and Sandelin, Albin},
  issn         = {2041-1723},
  language     = {eng},
  month        = {04},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies},
  url          = {http://dx.doi.org/10.1038/s41467-018-03766-z},
  doi          = {10.1038/s41467-018-03766-z},
  volume       = {9},
  year         = {2018},
}