TY - JOUR
T1 - Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies
AU - Boyd, Mette
AU - Thodberg, Malte
AU - Vitezic, Morana
AU - Lange, Jette Bornholdt
AU - Vitting-Seerup, Kristoffer
AU - Chen, Yun
AU - Coskun, Mehmet
AU - Li, Yuan
AU - Lo, Bobby Zhao Sheng
AU - Klausen, Pia
AU - Schweiger, Pawel
AU - Pedersen, Anders Gorm
AU - Rapin, Nicolas Philippe Jean-Pierre
AU - Skovgaard, Kerstin
AU - Dahlgaard, Katja
AU - Andersson, Robin
AU - Terkelsen, Thilde Bagger
AU - Lilje, Berit
AU - Troelsen, Jesper Thorvald
AU - Petersen, Andreas Munk
AU - Jensen, Kim Bak
AU - Gögenur, Ismail
AU - Thielsen, Peter
AU - Seidelin, Jakob Benedict
AU - Nielsen, Ole Haagen
AU - Bjerrum, Jacob Tveiten
AU - Sandelin, Albin Gustav
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-018-03766-z
DO - 10.1038/s41467-018-03766-z
M3 - Journal article
C2 - 29695774
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1661
ER -