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

Mette Boyd; Malte Thodberg; Morana Vitezic; Jette Bornholdt Lange; Kristoffer Vitting-Seerup; Yun Chen; Mehmet Coskun; Yuan Li; Bobby Zhao Sheng Lo; Pia Klausen; Pawel Schweiger; Anders Gorm Pedersen; Nicolas Philippe Jean-Pierre Rapin; Kerstin Skovgaard; Katja Dahlgaard; Robin Andersson; Thilde Bagger Terkelsen; Berit Lilje; Jesper Thorvald Troelsen; Andreas Munk Petersen; Kim Bak Jensen; Ismail Gögenur; Peter Thielsen; Jakob Benedict Seidelin; Ole Haagen Nielsen; Jacob Tveiten Bjerrum; Albin Gustav Sandelin

doi:10.1038/s41467-018-03766-z

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

Mette Boyd, Malte Thodberg, Morana Vitezic, Jette Bornholdt Lange, Kristoffer Vitting-Seerup, Yun Chen, Mehmet Coskun, Yuan Li, Bobby Zhao Sheng Lo, Pia Klausen, Pawel Schweiger, Anders Gorm Pedersen, Nicolas Philippe Jean-Pierre Rapin, Kerstin Skovgaard, Katja Dahlgaard, Robin Andersson, Thilde Bagger Terkelsen, Berit Lilje, Jesper Thorvald Troelsen, Andreas Munk PetersenKim Bak Jensen, Ismail Gögenur, Peter Thielsen, Jakob Benedict Seidelin, Ole Haagen Nielsen, Jacob Tveiten Bjerrum, Albin Gustav Sandelin

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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.

Original language	English
Article number	1661
Journal	Nature Communications
Volume	9
Number of pages	19
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-03766-z
Publication status	Published - 1 Dec 2018

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Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsiesFinal published version, 2.55 MBLicence: CC BY

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Boyd, M., Thodberg, M., Vitezic, M., Lange, J. B., Vitting-Seerup, K., Chen, Y., Coskun, M., Li, Y., Lo, B. Z. S., Klausen, P., Schweiger, P., Pedersen, A. G., Rapin, N. P. J.-P., Skovgaard, K., Dahlgaard, K., Andersson, R., Terkelsen, T. B., Lilje, B., Troelsen, J. T., ... Sandelin, A. G. (2018). Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies. Nature Communications, 9, Article 1661. https://doi.org/10.1038/s41467-018-03766-z

Boyd, M, Thodberg, M, Vitezic, M, Lange, JB, Vitting-Seerup, K, Chen, Y, Coskun, M, Li, Y, Lo, BZS, Klausen, P, Schweiger, P, Pedersen, AG, Rapin, NPJ-P, Skovgaard, K, Dahlgaard, K, Andersson, R, Terkelsen, TB, Lilje, B, Troelsen, JT, Petersen, AM , Jensen, KB , Gögenur, I, Thielsen, P, Seidelin, JB , Nielsen, OH , Bjerrum, JT & Sandelin, AG 2018, 'Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies', Nature Communications, vol. 9, 1661. https://doi.org/10.1038/s41467-018-03766-z

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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.",

author = "Mette Boyd and Malte Thodberg and Morana Vitezic and Lange, {Jette Bornholdt} and Kristoffer Vitting-Seerup and Yun Chen and Mehmet Coskun and Yuan Li and Lo, {Bobby Zhao Sheng} and Pia Klausen and Pawel Schweiger and Pedersen, {Anders Gorm} and Rapin, {Nicolas Philippe Jean-Pierre} and Kerstin Skovgaard and Katja Dahlgaard and Robin Andersson and Terkelsen, {Thilde Bagger} and Berit Lilje and Troelsen, {Jesper Thorvald} and Petersen, {Andreas Munk} and Jensen, {Kim Bak} and Ismail G{\"o}genur and Peter Thielsen and Seidelin, {Jakob Benedict} and Nielsen, {Ole Haagen} and Bjerrum, {Jacob Tveiten} and Sandelin, {Albin Gustav}",

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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 - 2018/12/1

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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.

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SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 1661

ER -

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

Abstract

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