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 - Bornholdt, Jette
AU - Vitting-Seerup, Kristoffer
AU - Chen, Yun
AU - Coshun, Mehmet
AU - Li, Yuan
AU - Sheng Lo, Bobby Zhao
AU - Klausen, Pia
AU - Schweiger, Pawel Jan
AU - Pedersen, Anders Gorm
AU - Rapin, Nicolas
AU - Skovgaard, Kerstin
AU - Dahlgaard, Katja
AU - Andersson, Robin
AU - Terkelsen, Thilde Bagger
AU - Lilje, Berit
AU - Troelsen, Jesper
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 - 2018/4/25
Y1 - 2018/4/25
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.
KW - Disease genetics
KW - Inflammatory bowel disease
KW - Transcriptional regulatory elements
KW - Transcriptomics
UR - https://rdcu.be/MxWZ
U2 - 10.1038/s41467-018-03766-z
DO - 10.1038/s41467-018-03766-z
M3 - Journal article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1661
ER -