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

Mette Boyd, Malte Thodberg, Morana Vitezic, Jette Bornholdt, Kristoffer Vitting-Seerup, Yun Chen, Mehmet Coshun, Yuan Li, Bobby Zhao Sheng Lo, Pia Klausen, Pawel Jan Schweiger, Anders Gorm Pedersen, Nicolas Rapin, Kerstin Skovgaard, Katja Dahlgaard, Robin Andersson, Thilde Bagger Terkelsen, Berit Lilje, Jesper Troelsen, Andreas Munk Petersen & 7 andre Kim Bak Jensen, Ismail Gögenur, Peter Thielsen, Jakob Benedict Seidelin, Ole Haagen Nielsen, Jacob Tveiten Bjerrum, Albin Gustav Sandelin

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
Artikelnummer1661 (2018)
TidsskriftNature Communications
Vol/bind9
ISSN2041-1723
DOI
StatusUdgivet - 25 apr. 2018

Citer dette

Boyd, M., Thodberg, M., Vitezic, M., Bornholdt, J., Vitting-Seerup, K., Chen, Y., ... Sandelin, A. G. (2018). Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies. Nature Communications, 9, [1661 (2018)]. https://doi.org/10.1038/s41467-018-03766-z
Boyd, Mette ; Thodberg, Malte ; Vitezic, Morana ; Bornholdt, Jette ; Vitting-Seerup, Kristoffer ; Chen, Yun ; Coshun, Mehmet ; Li, Yuan ; Sheng Lo, Bobby Zhao ; Klausen, Pia ; Schweiger, Pawel Jan ; Pedersen, Anders Gorm ; Rapin, Nicolas ; Skovgaard, Kerstin ; Dahlgaard, Katja ; Andersson, Robin ; Terkelsen, Thilde Bagger ; Lilje, Berit ; Troelsen, Jesper ; Petersen, Andreas Munk ; Jensen, Kim Bak ; Gögenur, Ismail ; Thielsen, Peter ; Seidelin, Jakob Benedict ; Nielsen, Ole Haagen ; Bjerrum, Jacob Tveiten ; Sandelin, Albin Gustav. / Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies. I: Nature Communications. 2018 ; Bind 9.
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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.",
keywords = "Disease genetics, Inflammatory bowel disease, Transcriptional regulatory elements, Transcriptomics",
author = "Mette Boyd and Malte Thodberg and Morana Vitezic and Jette Bornholdt and Kristoffer Vitting-Seerup and Yun Chen and Mehmet Coshun and Yuan Li and {Sheng Lo}, {Bobby Zhao} and Pia Klausen and Schweiger, {Pawel Jan} and Pedersen, {Anders Gorm} and Nicolas Rapin and Kerstin Skovgaard and Katja Dahlgaard and Robin Andersson and Terkelsen, {Thilde Bagger} and Berit Lilje and Jesper Troelsen 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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Boyd, M, Thodberg, M, Vitezic, M, Bornholdt, J, Vitting-Seerup, K, Chen, Y, Coshun, M, Li, Y, Sheng Lo, BZ, Klausen, P, Schweiger, PJ, Pedersen, AG, Rapin, N, Skovgaard, K, Dahlgaard, K, Andersson, R, Terkelsen, TB, Lilje, B, Troelsen, J, 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, bind 9, 1661 (2018). https://doi.org/10.1038/s41467-018-03766-z

Characterization of the enhancer and promoter landscape of inflammatory bowel disease from human colon biopsies. / Boyd, Mette; Thodberg, Malte; Vitezic, Morana; Bornholdt, Jette; Vitting-Seerup, Kristoffer; Chen, Yun; Coshun, Mehmet; Li, Yuan; Sheng Lo, Bobby Zhao; Klausen, Pia; Schweiger, Pawel Jan; Pedersen, Anders Gorm; Rapin, Nicolas; Skovgaard, Kerstin; Dahlgaard, Katja; Andersson, Robin; Terkelsen, Thilde Bagger; Lilje, Berit; Troelsen, Jesper; Petersen, Andreas Munk; Jensen, Kim Bak; Gögenur, Ismail; Thielsen, Peter; Seidelin, Jakob Benedict; Nielsen, Ole Haagen; Bjerrum, Jacob Tveiten ; Sandelin, Albin Gustav.

I: Nature Communications, Bind 9, 1661 (2018), 25.04.2018.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

VL - 9

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 1661 (2018)

ER -